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20211941 | Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition. | Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of Nrf2 is known to protect neurons. In previous work, our laboratory found that Nrf2 protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific Nrf2 overexpression provide protection from neurotoxicity in vivo. GFAP-Nrf2 transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced Nrf2 response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing Nrf2 that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic Nrf2 response and Nrf2 preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. | Astrocyte-specific overexpression of /"Nrf2"/ protects striatal neurons from mitochondrial complex II inhibition. | /"Nuclear factor E2-related factor 2"/ (/"Nrf2"/) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of /"Nrf2"/ is known to protect neurons. In previous work, our laboratory found that /"Nrf2"/ protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific /"Nrf2"/ overexpression provide protection from /"neurotoxicity"/ in vivo. GFAP-/"Nrf2"/ transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced /"Nrf2"/ response to lesioning that attenuated the ensuing /"neurotoxicity"/. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing /"Nrf2"/ that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic /"Nrf2"/ response and /"Nrf2"/ preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. | [
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20211941 | Astrocyte-specific overexpression of Nrf2 protects striatal neurons from mitochondrial complex II inhibition. | Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of Nrf2 is known to protect neurons. In previous work, our laboratory found that Nrf2 protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific Nrf2 overexpression provide protection from neurotoxicity in vivo. GFAP-Nrf2 transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced Nrf2 response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing Nrf2 that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic Nrf2 response and Nrf2 preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. | Astrocyte-specific overexpression of /"Nrf2"/ protects striatal neurons from mitochondrial complex II inhibition. | /"Nuclear factor E2-related factor 2"/ (/"Nrf2"/) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of /"Nrf2"/ is known to protect neurons. In previous work, our laboratory found that /"Nrf2"/ protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific /"Nrf2"/ overexpression provide protection from neurotoxicity in vivo. GFAP-/"Nrf2"/ transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced /"Nrf2"/ response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing /"Nrf2"/ that differentiate into astrocytes after grafting also significantly reduced malonate /"toxicity"/. Overall, these data establish that enhanced astrocytic /"Nrf2"/ response and /"Nrf2"/ preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. | [
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20220260 | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR532 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with /"asthma"/ and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, /"CCR5"/ <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for /"asthma"/ and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with /"asthma"/ and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed /"asthma"/ (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in /"CCR5"/ were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with /"asthma"/, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of /"asthma"/. The previous association of the CCR532 deletion with protection from childhood /"asthma"/ appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | [
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20220260 | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR532 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with /"asthma"/ and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, /"CCR3"/, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for /"asthma"/ and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with /"asthma"/ and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed /"asthma"/ (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in /"CCR3"/, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with /"asthma"/, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of /"asthma"/. The previous association of the CCR532 deletion with protection from childhood /"asthma"/ appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | [
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20220260 | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR532 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with /"asthma"/ and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for /"asthma"/ and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with /"asthma"/ and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed /"asthma"/ (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (/"SPT 3"/ mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with /"asthma"/, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of /"asthma"/. The previous association of the CCR532 deletion with protection from childhood /"asthma"/ appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | [
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},
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"entity_id": "1234",
"entity_type": "Gene",
"text_name": "CCR5"
},
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},
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] | {
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"entity_type": "Gene",
"text_name": "SPT 3"
} | {
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"end_idx": "1652",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
} | No |
20220260 | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR532 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with /"asthma"/ and atopy. | BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single-nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for /"asthma"/ and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with /"asthma"/ and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed /"asthma"/ (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (/"SPT 3"/ mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with /"asthma"/, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of /"asthma"/. The previous association of the CCR532 deletion with protection from childhood /"asthma"/ appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene. | [
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} | {
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"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
} | No |
20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), /"fms-like tyrosine kinase 4"/ rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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},
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"text_name": "vascular endothelial growth factor C"
},
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"entity_id": "D011225",
"entity_type": "Disease",
"text_name": "preeclampsia"
} | Yes |
20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; /"endoglin"/) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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"text_name": "preeclampsia"
} | Yes |
20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; /"fms-like tyrosine kinase 1"/ and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the /"fms-like tyrosine kinase 1"/ rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the /"fms-like tyrosine kinase 1"/ rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the /"fms-like tyrosine kinase 1 and vascular endothelial growth factor C"/ genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (/"vascular endothelial growth factor A, B"/, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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} | Yes |
20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (/"vascular endothelial growth factor A, B"/, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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} | Yes |
20223440 | Allelic variations in angiogenic pathway genes are associated with preeclampsia. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and preeclampsia. STUDY DESIGN: Data for cases with preeclampsia and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and preeclampsia; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the vascular endothelial growth factor C rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with preeclampsia. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and vascular endothelial growth factor C rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with preeclampsia. CONCLUSION: Allelic variations in the fms-like tyrosine kinase 1 and vascular endothelial growth factor C genes are associated with preeclampsia in both ethnic groups. | Allelic variations in angiogenic pathway genes are associated with /"preeclampsia"/. | OBJECTIVE: This study investigates the association of allelic variation in angiogenic pathway genes and /"preeclampsia"/. STUDY DESIGN: Data for cases with /"preeclampsia"/ and term control subjects were collected prospectively. Maternal DNA was extracted, and 124 tagging single nucleotide polymorphisms in 6 genes (vascular endothelial growth factor A, B, and C; fms-like tyrosine kinase 1 and 4; endoglin) were genotyped. Multivariable logistic regression was used to evaluate the association between tagging single nucleotide polymorphisms and /"preeclampsia"/; data were controlled for age. All models were evaluated in black women and white women separately. Haplotype analyses were performed. RESULTS: We analyzed data from 606 women (489 black women [184 cases] and 117 white women [32 cases]). In black women, the fms-like tyrosine kinase 1 rs12584067 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.01-2.36; P=.05) and rs7335588 (OR, 1.61; 95% CI, 1.06-2.43; P=.01) and the /"vascular endothelial growth factor C"/ rs1485766 (OR, 1.56; 95% CI, 1.05-2.30; P=.03) and rs6838834 (OR, 1.60; 95% CI, 1.05-2.45; P=.03) single nucleotide polymorphisms were associated with /"preeclampsia"/. In white women, the fms-like tyrosine kinase 1 rs722503 (OR, 2.12; 95% CI, 1.07-4.19; P=.03), fms-like tyrosine kinase 4 rs307826 (OR, 3.06; 95% CI, 1.18-7.91; P=.01), and /"vascular endothelial growth factor C"/ rs7664413 (OR, 2.04; 95% CI, 0.99-4.17; P=.04) single nucleotide polymorphisms were associated with /"preeclampsia"/. CONCLUSION: Allelic variations in the /"fms-like tyrosine kinase 1 and vascular endothelial growth factor C"/ genes are associated with /"preeclampsia"/ in both ethnic groups. | [
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"entity_type": "Disease",
"text_name": "preeclampsia"
},
{
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"entity_id": "D011225",
"entity_type": "Disease",
"text_name": "preeclampsia"
},
{
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"end_idx": "480",
"entity_id": "2022",
"entity_type": "Gene",
"text_name": "endoglin"
},
{
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"entity_type": "Gene",
"text_name": "fms-like tyrosine kinase 1"
},
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},
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},
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"entity_type": "Gene",
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},
{
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"entity_type": "Gene",
"text_name": "vascular endothelial growth factor A, B"
},
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"text_name": "vascular endothelial growth factor A, B"
},
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},
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},
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}
] | {
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} | {
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"entity_id": "D011225",
"entity_type": "Disease",
"text_name": "preeclampsia"
} | Yes |
20236202 | Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. | BACKGROUND: Recessive X-linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. RXLI is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of STS gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the STS gene by polymerase chain reaction in 40 patients with clinical features of RXLI. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions. | Analysis of the /"STS"/ gene in 40 patients with recessive /"X-linked ichthyosis"/: a high frequency of partial deletions in a Spanish population. | BACKGROUND: Recessive X-linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. RXLI is caused by a deficiency in /"steroid sulphatase"/ (/"STS"/), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of /"STS"/ gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the /"STS"/ gene by polymerase chain reaction in 40 patients with clinical features of RXLI. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions. | [
{
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"end_idx": "74",
"entity_id": "D016114",
"entity_type": "Disease",
"text_name": "X-linked ichthyosis"
},
{
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"end_idx": "180",
"entity_id": "D040181",
"entity_type": "Disease",
"text_name": "Recessive X-linked ichthyosis"
},
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"entity_id": "D040181",
"entity_type": "Disease",
"text_name": "RXLI"
},
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},
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},
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},
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"text_name": "RXLI"
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"text_name": "STS"
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},
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"entity_id": "412",
"entity_type": "Gene",
"text_name": "STS"
}
] | {
"begin_idx": "364",
"end_idx": "382",
"entity_id": "412",
"entity_type": "Gene",
"text_name": "steroid sulphatase"
} | {
"begin_idx": "55",
"end_idx": "74",
"entity_id": "D016114",
"entity_type": "Disease",
"text_name": "X-linked ichthyosis"
} | Yes |
20236202 | Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. | BACKGROUND: Recessive X-linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. RXLI is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of STS gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the STS gene by polymerase chain reaction in 40 patients with clinical features of RXLI. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions. | Analysis of the /"STS"/ gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population. | BACKGROUND: /"Recessive X-linked ichthyosis"/ (/"RXLI"/) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. /"RXLI"/ is caused by a deficiency in /"steroid sulphatase"/ (/"STS"/), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of /"STS"/ gene in cases of /"RXLI"/ prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the /"STS"/ gene by polymerase chain reaction in 40 patients with clinical features of /"RXLI"/. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening /"RXLI"/ in the population studied here. No correlation was found between phenotype and the extent of the deletions. | [
{
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"end_idx": "74",
"entity_id": "D016114",
"entity_type": "Disease",
"text_name": "X-linked ichthyosis"
},
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"end_idx": "180",
"entity_id": "D040181",
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},
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"text_name": "RXLI"
},
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"entity_type": "Disease",
"text_name": "RXLI"
},
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"entity_id": "D040181",
"entity_type": "Disease",
"text_name": "RXLI"
},
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"entity_id": "D040181",
"entity_type": "Disease",
"text_name": "RXLI"
},
{
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"entity_type": "Gene",
"text_name": "STS"
},
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"entity_type": "Gene",
"text_name": "steroid sulphatase"
},
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"text_name": "STS"
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"text_name": "STS"
},
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"entity_id": "412",
"entity_type": "Gene",
"text_name": "STS"
}
] | {
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"end_idx": "746",
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"entity_type": "Gene",
"text_name": "STS"
} | {
"begin_idx": "822",
"end_idx": "826",
"entity_id": "D040181",
"entity_type": "Disease",
"text_name": "RXLI"
} | No |
20237358 | Significantly elevated concentration of plasma monocyte chemotactic protein 1 of patients with pelvic inflammatory disease. | Our goal was to compare the expression of plasma monocyte chemotactic protein 1 (MCP-1) and the gene polymorphism in patients with pelvic inflammatory disease (PID) and healthy controls. The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively, used to measure the plasma MCP-1 level and MCP-1 polymorphism in 70 healthy controls and in 64 patients with PID before and after they received routine treatment protocols. We found plasma MCP-1 was significantly elevated in patients with PID compared to that in normal controls and decreased significantly compared to that in patients with PID after they received treatment. The increased expression of plasma MCP-1 was significantly correlated with the cell counts of white blood cells (WBCs) in blood and the level of plasma C-reactive protein (CRP) of patients with PID before they received treatment. There was no association between MCP-1 -2518G/A SNP and its gene expression levels and PID susceptibility. Elevated plasma MCP-1 could be a biological marker for the diagnosis and to be a new strategy for target therapy of pelvic inflammatory disease. | Significantly elevated concentration of plasma /"monocyte chemotactic protein 1"/ of patients with /"pelvic inflammatory disease"/. | Our goal was to compare the expression of plasma /"monocyte chemotactic protein 1"/ (/"MCP-1"/) and the gene polymorphism in patients with /"pelvic inflammatory disease"/ (/"PID"/) and healthy controls. The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively, used to measure the plasma /"MCP-1"/ level and /"MCP-1"/ polymorphism in 70 healthy controls and in 64 patients with /"PID"/ before and after they received routine treatment protocols. We found plasma /"MCP-1"/ was significantly elevated in patients with /"PID"/ compared to that in normal controls and decreased significantly compared to that in patients with /"PID"/ after they received treatment. The increased expression of plasma /"MCP-1"/ was significantly correlated with the cell counts of white blood cells (WBCs) in blood and the level of plasma C-reactive protein (CRP) of patients with /"PID"/ before they received treatment. There was no association between /"MCP-1"/ -2518G/A SNP and its gene expression levels and /"PID"/ susceptibility. Elevated plasma /"MCP-1"/ could be a biological marker for the diagnosis and to be a new strategy for target therapy of /"pelvic inflammatory disease"/. | [
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},
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"text_name": "CRP"
},
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"text_name": "monocyte chemotactic protein 1"
},
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"entity_id": "6347",
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},
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},
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},
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},
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"entity_id": "6347",
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"text_name": "MCP-1"
},
{
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"end_idx": "1193",
"entity_id": "6347",
"entity_type": "Gene",
"text_name": "MCP-1"
}
] | {
"begin_idx": "47",
"end_idx": "77",
"entity_id": "6347",
"entity_type": "Gene",
"text_name": "monocyte chemotactic protein 1"
} | {
"begin_idx": "95",
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"entity_id": "D000292",
"entity_type": "Disease",
"text_name": "pelvic inflammatory disease"
} | Yes |
20237358 | Significantly elevated concentration of plasma monocyte chemotactic protein 1 of patients with pelvic inflammatory disease. | Our goal was to compare the expression of plasma monocyte chemotactic protein 1 (MCP-1) and the gene polymorphism in patients with pelvic inflammatory disease (PID) and healthy controls. The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively, used to measure the plasma MCP-1 level and MCP-1 polymorphism in 70 healthy controls and in 64 patients with PID before and after they received routine treatment protocols. We found plasma MCP-1 was significantly elevated in patients with PID compared to that in normal controls and decreased significantly compared to that in patients with PID after they received treatment. The increased expression of plasma MCP-1 was significantly correlated with the cell counts of white blood cells (WBCs) in blood and the level of plasma C-reactive protein (CRP) of patients with PID before they received treatment. There was no association between MCP-1 -2518G/A SNP and its gene expression levels and PID susceptibility. Elevated plasma MCP-1 could be a biological marker for the diagnosis and to be a new strategy for target therapy of pelvic inflammatory disease. | Significantly elevated concentration of plasma monocyte chemotactic protein 1 of patients with /"pelvic inflammatory disease"/. | Our goal was to compare the expression of plasma monocyte chemotactic protein 1 (MCP-1) and the gene polymorphism in patients with /"pelvic inflammatory disease"/ (/"PID"/) and healthy controls. The enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were, respectively, used to measure the plasma MCP-1 level and MCP-1 polymorphism in 70 healthy controls and in 64 patients with /"PID"/ before and after they received routine treatment protocols. We found plasma MCP-1 was significantly elevated in patients with /"PID"/ compared to that in normal controls and decreased significantly compared to that in patients with /"PID"/ after they received treatment. The increased expression of plasma MCP-1 was significantly correlated with the cell counts of white blood cells (WBCs) in blood and the level of plasma /"C-reactive protein"/ (/"CRP"/) of patients with /"PID"/ before they received treatment. There was no association between MCP-1 -2518G/A SNP and its gene expression levels and /"PID"/ susceptibility. Elevated plasma MCP-1 could be a biological marker for the diagnosis and to be a new strategy for target therapy of /"pelvic inflammatory disease"/. | [
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},
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"text_name": "pelvic inflammatory disease"
},
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"text_name": "C-reactive protein"
},
{
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"entity_id": "1401",
"entity_type": "Gene",
"text_name": "CRP"
},
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},
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},
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"entity_id": "6347",
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"text_name": "MCP-1"
},
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"text_name": "MCP-1"
},
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},
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},
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"entity_id": "6347",
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"text_name": "MCP-1"
},
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"entity_id": "6347",
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"text_name": "MCP-1"
},
{
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"end_idx": "1193",
"entity_id": "6347",
"entity_type": "Gene",
"text_name": "MCP-1"
}
] | {
"begin_idx": "1007",
"end_idx": "1010",
"entity_id": "1401",
"entity_type": "Gene",
"text_name": "CRP"
} | {
"begin_idx": "255",
"end_idx": "282",
"entity_id": "D000292",
"entity_type": "Disease",
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20237592 | Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | Effect of long-term treatment with urocortin on the activity of somatic /"angiotensin-converting enzyme"/ in spontaneously /"hypertensive"/ rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue /"angiotensin-converting enzyme"/ (/"ACE"/) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic /"ACE"/ (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously /"hypertensive"/ rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the /"ACE"/ inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum /"ACE"/ activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | [
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20237592 | Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | Effect of long-term treatment with /"urocortin"/ on the activity of somatic angiotensin-converting enzyme in spontaneously /"hypertensive"/ rats. | Our previous acute study on /"urocortin"/ (/"Ucn"/) demonstrated that /"Ucn"/ altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with /"Ucn"/ on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of /"Ucn"/ in spontaneously /"hypertensive"/ rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by /"Ucn"/, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by /"Ucn"/, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after /"Ucn"/ treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term /"Ucn"/ administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of /"Ucn"/. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of /"Ucn"/ via the activation of the ERK1/2 pathway. | [
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20237592 | Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the /"corticotropin-releasing factor"/ (/"CRF"/) blocker astressin and the /"extracellular signal-regulated kinase 1/2"/ (/"ERK1/2"/) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the /"ERK1/2"/ pathway. | [
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20237592 | Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | Effect of long-term treatment with urocortin on the activity of somatic /"angiotensin-converting enzyme"/ in spontaneously hypertensive rats. | Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue /"angiotensin-converting enzyme"/ (/"ACE"/) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic /"ACE"/ (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the /"ACE"/ inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum /"ACE"/ activity and SBP. Pretreatment with the /"corticotropin-releasing factor"/ (/"CRF"/) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway. | [
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20350254 | Interleukin-18 gene polymorphism and markers of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study. | BACKGROUND AND AIM: Interleukin-18 (IL-18) is a pro-atherosclerotic cytokine. We wanted to evaluate whether IL-18 gene polymorphism associates independently of risk factors, with early subclinical markers of atherosclerosis (intima-media thickness (IMT), coronary artery compliance (CAC), and flow-mediated dilatation (FMD)) in a population of young healthy Caucasian adults. METHODS: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men). RESULTS: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the IL-18 gene. According to adjusted analysis of variance, the IL-18 gene polymorphism did not associate with subclinical atherosclerosis in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed. CONCLUSIONS: Among all study subjects, the polymorphism of the IL-18 gene is not associated with subclinical markers of atherosclerosis. However, among men one major IL-18 haplotype seemed to associate with substantially lower IMT values. | /"Interleukin-18"/ gene polymorphism and markers of subclinical /"atherosclerosis"/. The Cardiovascular Risk in Young Finns Study. | BACKGROUND AND AIM: /"Interleukin-18"/ (/"IL-18"/) is a pro-/"atherosclerotic"/ cytokine. We wanted to evaluate whether /"IL-18"/ gene polymorphism associates independently of risk factors, with early subclinical markers of /"atherosclerosis"/ (intima-media thickness (IMT), coronary artery compliance (CAC), and flow-mediated dilatation (FMD)) in a population of young healthy Caucasian adults. METHODS: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men). RESULTS: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the /"IL-18"/ gene. According to adjusted analysis of variance, the /"IL-18"/ gene polymorphism did not associate with subclinical /"atherosclerosis"/ in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed. CONCLUSIONS: Among all study subjects, the polymorphism of the /"IL-18"/ gene is not associated with subclinical markers of /"atherosclerosis"/. However, among men one major /"IL-18"/ haplotype seemed to associate with substantially lower IMT values. | [
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20350254 | Interleukin-18 gene polymorphism and markers of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study. | BACKGROUND AND AIM: Interleukin-18 (IL-18) is a pro-atherosclerotic cytokine. We wanted to evaluate whether IL-18 gene polymorphism associates independently of risk factors, with early subclinical markers of atherosclerosis (intima-media thickness (IMT), coronary artery compliance (CAC), and flow-mediated dilatation (FMD)) in a population of young healthy Caucasian adults. METHODS: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men). RESULTS: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the IL-18 gene. According to adjusted analysis of variance, the IL-18 gene polymorphism did not associate with subclinical atherosclerosis in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed. CONCLUSIONS: Among all study subjects, the polymorphism of the IL-18 gene is not associated with subclinical markers of atherosclerosis. However, among men one major IL-18 haplotype seemed to associate with substantially lower IMT values. | /"Interleukin-18"/ gene polymorphism and markers of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study. | BACKGROUND AND AIM: /"Interleukin-18"/ (/"IL-18"/) is a pro-atherosclerotic cytokine. We wanted to evaluate whether /"IL-18"/ gene polymorphism associates independently of risk factors, with early subclinical markers of atherosclerosis (intima-media thickness (IMT), coronary artery compliance (CAC), and /"flow-mediated dilatation"/ (/"FMD"/)) in a population of young healthy Caucasian adults. METHODS: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men). RESULTS: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the /"IL-18"/ gene. According to adjusted analysis of variance, the /"IL-18"/ gene polymorphism did not associate with subclinical atherosclerosis in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed. CONCLUSIONS: Among all study subjects, the polymorphism of the /"IL-18"/ gene is not associated with subclinical markers of atherosclerosis. However, among men one major /"IL-18"/ haplotype seemed to associate with substantially lower IMT values. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | /"RASSF1A"/ polymorphism in /"familial breast cancer"/. | Inactivation or loss of the tumour suppressor /"Ras associated domain family 1 isoform A"/ (/"RASSF1A"/) allele has been described in /"breast cancer"/. Recently, a missense polymorphism predicting p.A331S in /"RASSF1A"/ was associated with an increased risk of /"breast cancer"/ and early-onset /"breast cancer"/ in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S /"RASSF1A"/ in 854 independent, familial, white /"breast cancer"/ patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The /"RASSF1A"/ p.A331S variant was not more common in the /"familial breast cancer"/ cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the /"RASSF1A"/ p.A331S polymorphism is not confirmed as a significant germline contributor to /"familial breast cancer"/ susceptibility. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | RASSF1A polymorphism in /"familial breast cancer"/. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in /"breast cancer"/. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of /"breast cancer"/ and early-onset /"breast cancer"/ in /"BRCA1"/ and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white /"breast cancer"/ patients (645 BRCA mutation negative, 119 /"BRCA1"/ and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the /"familial breast cancer"/ cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the /"BRCA1"/ (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to /"familial breast cancer"/ susceptibility. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | RASSF1A polymorphism in /"familial breast cancer"/. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in /"breast cancer"/. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of /"breast cancer"/ and early-onset /"breast cancer"/ in BRCA1 and /"BRCA2"/ mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white /"breast cancer"/ patients (645 BRCA mutation negative, 119 BRCA1 and 90 /"BRCA2"/ positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the /"familial breast cancer"/ cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), /"BRCA2"/ (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to /"familial breast cancer"/ susceptibility. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | /"RASSF1A"/ polymorphism in familial breast cancer. | Inactivation or loss of the /"tumour"/ suppressor /"Ras associated domain family 1 isoform A"/ (/"RASSF1A"/) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in /"RASSF1A"/ was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S /"RASSF1A"/ in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The /"RASSF1A"/ p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the /"RASSF1A"/ p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the /"tumour"/ suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and /"BRCA2"/ mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 /"BRCA2"/ positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), /"BRCA2"/ (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | [
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20361264 | RASSF1A polymorphism in familial breast cancer. | Inactivation or loss of the tumour suppressor Ras associated domain family 1 isoform A (RASSF1A) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in RASSF1A was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S RASSF1A in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The RASSF1A p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | /"RASSF1A"/ polymorphism in familial breast cancer. | Inactivation or loss of the /"tumour"/ suppressor /"Ras associated domain family 1 isoform A"/ (/"RASSF1A"/) allele has been described in breast cancer. Recently, a missense polymorphism predicting p.A331S in /"RASSF1A"/ was associated with an increased risk of breast cancer and early-onset breast cancer in BRCA1 and BRCA2 mutation carriers. We genotyped p.A331S /"RASSF1A"/ in 854 independent, familial, white breast cancer patients (645 BRCA mutation negative, 119 BRCA1 and 90 BRCA2 positive) and compared the genotype in 331 healthy women. The /"RASSF1A"/ p.A331S variant was not more common in the familial breast cancer cases than in the controls (P = 0.27). Subset analysis demonstrated no association in the BRCA1 (P = 0.26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the /"RASSF1A"/ p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility. | [
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20373279 | FTO genotype and weight gain in obese and normal weight adults from a Norwegian population based cohort (the HUNT study). | The fat mass and obesity associated gene ( FTO) is associated with bodyweight and obesity. The aim of this study was to investigate if FTO genotype affects weight gain in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI>= 35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. FTO genotype was assessed by genotyping of the SNP rs1421085. A strong association between FTO and obesity was found, consistent with an additive gene effect. Cases had an average weight gain of 11.1 kg, whereas controls had an average weight gain of 1.4 kg. Genotype was neither associated with weight gain in obese, nor controls. Cases had an average weight gain of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average weight gain of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, FTO was associated with obesity, but not with weight gain in adults during 11 years of follow-up. | /"FTO"/ genotype and /"weight gain"/ in obese and normal weight adults from a Norwegian population based cohort (the HUNT study). | The fat mass and obesity associated gene ( /"FTO"/) is associated with bodyweight and obesity. The aim of this study was to investigate if /"FTO"/ genotype affects /"weight gain"/ in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI>= 35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. /"FTO"/ genotype was assessed by genotyping of the SNP rs1421085. A strong association between /"FTO"/ and obesity was found, consistent with an additive gene effect. Cases had an average /"weight gain"/ of 11.1 kg, whereas controls had an average /"weight gain"/ of 1.4 kg. Genotype was neither associated with /"weight gain"/ in obese, nor controls. Cases had an average /"weight gain"/ of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average /"weight gain"/ of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, /"FTO"/ was associated with obesity, but not with /"weight gain"/ in adults during 11 years of follow-up. | [
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20373279 | FTO genotype and weight gain in obese and normal weight adults from a Norwegian population based cohort (the HUNT study). | The fat mass and obesity associated gene ( FTO) is associated with bodyweight and obesity. The aim of this study was to investigate if FTO genotype affects weight gain in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI>= 35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. FTO genotype was assessed by genotyping of the SNP rs1421085. A strong association between FTO and obesity was found, consistent with an additive gene effect. Cases had an average weight gain of 11.1 kg, whereas controls had an average weight gain of 1.4 kg. Genotype was neither associated with weight gain in obese, nor controls. Cases had an average weight gain of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average weight gain of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, FTO was associated with obesity, but not with weight gain in adults during 11 years of follow-up. | /"FTO"/ genotype and weight gain in /"obese"/ and normal weight adults from a Norwegian population based cohort (the HUNT study). | The fat mass and /"obesity"/ associated gene ( /"FTO"/) is associated with bodyweight and /"obesity"/. The aim of this study was to investigate if /"FTO"/ genotype affects weight gain in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI>= 35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. /"FTO"/ genotype was assessed by genotyping of the SNP rs1421085. A strong association between /"FTO"/ and /"obesity"/ was found, consistent with an additive gene effect. Cases had an average weight gain of 11.1 kg, whereas controls had an average weight gain of 1.4 kg. Genotype was neither associated with weight gain in /"obese"/, nor controls. Cases had an average weight gain of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average weight gain of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, /"FTO"/ was associated with /"obesity"/, but not with weight gain in adults during 11 years of follow-up. | [
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20377893 | Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1. | BACKGROUND: MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility. METHODS: Nine single nucleotide polymorphisms (SNPs) in the MYG1 locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). MYG1 expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture. RESULTS: Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher MYG1 mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database. CONCLUSIONS: Our study demonstrated that both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the MYG1 gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo. | Promoter polymorphism -119C/G in /"MYG1"/ (/"C12orf10"/) gene is related to /"vitiligo"/ susceptibility and Arg4Gln affects mitochondrial entrance of /"Myg1"/. | BACKGROUND: /"MYG1"/ (/"Melanocyte proliferating gene 1"/, also /"C12orf10"/ in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that /"MYG1"/ mRNA expression is elevated in the skin of /"vitiligo"/ patients. Our aim was to examine nine known polymorphisms in the /"MYG1"/ gene, to investigate their functionality, and to study their association with /"vitiligo"/ susceptibility. METHODS: Nine single nucleotide polymorphisms (SNPs) in the /"MYG1"/ locus were investigated by SNPlex assay and/or sequencing in /"vitiligo"/ patients (n = 124) and controls (n = 325). /"MYG1"/ expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture. RESULTS: Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher /"MYG1"/ mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in /"vitiligo"/ patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the /"vitiligo"/ revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active /"vitiligo"/ (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged /"Myg1"/ protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that /"Myg1"/ 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database. CONCLUSIONS: Our study demonstrated that both /"MYG1"/ promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of /"Myg1"/ have a functional impact on the regulation of the /"MYG1"/ gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing /"vitiligo"/. | [
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20383754 | Vitamin D receptor polymorphisms in secondary hyperparathyroidism after Scopinaro's biliopancreatic diversion. | BACKGROUND: Secondary hyperparathyroidism is a frequent metabolic complication of bariatric surgery. Individual differences in calcium absorption determine chronic secondary hyperparathyroidism after biliopancreatic diversion in half of the patients who have normal levels of 25-hydroxyvitamin D. We aimed to evaluate if certain vitamin D receptor polymorphisms may be responsible for the latter. Cases and controls study including 57 patients after biliopancreatic diversion with a mean serum 25-hydroxyvitamin D above 20 ng/mL, separated into those with secondary hyperparathyroidism (n = 26, cases) and those without it (n = 31, controls). METHODS: Genotyping for restriction-length-fragment polymorphisms of the vitamin D receptor gene was carried out for FOK1, BSM1, APA1, and TAQ1, and haplotype structure was also constructed. RESULTS: There were no differences in the allelic or genotypes distribution of the four studied polymorphisms between patients and controls (P = 0.352 and P = 0.301 for FOK1, P = 0.733 and P = 0.924 for BSM1, P = 0.974 and P = 0.992 for APA1, and P = 0.995 and P = 0.928 for TAQ1, respectively). Haplotype analysis showed no differences between patients and controls (P = 0.495 for BAT, P = 1.000 for BAt, P = 0.508 for Bat and P = 0.924 for bAT haplotypes, respectively). Furthermore, haplotypes were not associated with serum PTH levels or with the ratio between serum PTH and 25-hydroxyvitamin D levels. CONCLUSION: Chronic secondary hyperparathyroidism after biliopancreatic diversion in patients with normal levels of 25-hydroxyvitamin D is not dependent on vitamin D receptor gene polymorphisms. | /"Vitamin D receptor"/ polymorphisms in /"secondary hyperparathyroidism"/ after Scopinaro's biliopancreatic diversion. | BACKGROUND: /"Secondary hyperparathyroidism"/ is a frequent metabolic complication of bariatric surgery. Individual differences in calcium absorption determine chronic /"secondary hyperparathyroidism"/ after biliopancreatic diversion in half of the patients who have normal levels of 25-hydroxyvitamin D. We aimed to evaluate if certain /"vitamin D receptor"/ polymorphisms may be responsible for the latter. Cases and controls study including 57 patients after biliopancreatic diversion with a mean serum 25-hydroxyvitamin D above 20 ng/mL, separated into those with /"secondary hyperparathyroidism"/ (n = 26, cases) and those without it (n = 31, controls). METHODS: Genotyping for restriction-length-fragment polymorphisms of the /"vitamin D receptor"/ gene was carried out for FOK1, BSM1, APA1, and TAQ1, and haplotype structure was also constructed. RESULTS: There were no differences in the allelic or genotypes distribution of the four studied polymorphisms between patients and controls (P = 0.352 and P = 0.301 for FOK1, P = 0.733 and P = 0.924 for BSM1, P = 0.974 and P = 0.992 for APA1, and P = 0.995 and P = 0.928 for TAQ1, respectively). Haplotype analysis showed no differences between patients and controls (P = 0.495 for BAT, P = 1.000 for BAt, P = 0.508 for Bat and P = 0.924 for bAT haplotypes, respectively). Furthermore, haplotypes were not associated with serum PTH levels or with the ratio between serum PTH and 25-hydroxyvitamin D levels. CONCLUSION: Chronic /"secondary hyperparathyroidism"/ after biliopancreatic diversion in patients with normal levels of 25-hydroxyvitamin D is not dependent on /"vitamin D receptor"/ gene polymorphisms. | [
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20383754 | Vitamin D receptor polymorphisms in secondary hyperparathyroidism after Scopinaro's biliopancreatic diversion. | BACKGROUND: Secondary hyperparathyroidism is a frequent metabolic complication of bariatric surgery. Individual differences in calcium absorption determine chronic secondary hyperparathyroidism after biliopancreatic diversion in half of the patients who have normal levels of 25-hydroxyvitamin D. We aimed to evaluate if certain vitamin D receptor polymorphisms may be responsible for the latter. Cases and controls study including 57 patients after biliopancreatic diversion with a mean serum 25-hydroxyvitamin D above 20 ng/mL, separated into those with secondary hyperparathyroidism (n = 26, cases) and those without it (n = 31, controls). METHODS: Genotyping for restriction-length-fragment polymorphisms of the vitamin D receptor gene was carried out for FOK1, BSM1, APA1, and TAQ1, and haplotype structure was also constructed. RESULTS: There were no differences in the allelic or genotypes distribution of the four studied polymorphisms between patients and controls (P = 0.352 and P = 0.301 for FOK1, P = 0.733 and P = 0.924 for BSM1, P = 0.974 and P = 0.992 for APA1, and P = 0.995 and P = 0.928 for TAQ1, respectively). Haplotype analysis showed no differences between patients and controls (P = 0.495 for BAT, P = 1.000 for BAt, P = 0.508 for Bat and P = 0.924 for bAT haplotypes, respectively). Furthermore, haplotypes were not associated with serum PTH levels or with the ratio between serum PTH and 25-hydroxyvitamin D levels. CONCLUSION: Chronic secondary hyperparathyroidism after biliopancreatic diversion in patients with normal levels of 25-hydroxyvitamin D is not dependent on vitamin D receptor gene polymorphisms. | Vitamin D receptor polymorphisms in /"secondary hyperparathyroidism"/ after Scopinaro's biliopancreatic diversion. | BACKGROUND: /"Secondary hyperparathyroidism"/ is a frequent metabolic complication of bariatric surgery. Individual differences in calcium absorption determine chronic /"secondary hyperparathyroidism"/ after biliopancreatic diversion in half of the patients who have normal levels of 25-hydroxyvitamin D. We aimed to evaluate if certain vitamin D receptor polymorphisms may be responsible for the latter. Cases and controls study including 57 patients after biliopancreatic diversion with a mean serum 25-hydroxyvitamin D above 20 ng/mL, separated into those with /"secondary hyperparathyroidism"/ (n = 26, cases) and those without it (n = 31, controls). METHODS: Genotyping for restriction-length-fragment polymorphisms of the vitamin D receptor gene was carried out for FOK1, BSM1, /"APA1"/, and TAQ1, and haplotype structure was also constructed. RESULTS: There were no differences in the allelic or genotypes distribution of the four studied polymorphisms between patients and controls (P = 0.352 and P = 0.301 for FOK1, P = 0.733 and P = 0.924 for BSM1, P = 0.974 and P = 0.992 for /"APA1"/, and P = 0.995 and P = 0.928 for TAQ1, respectively). Haplotype analysis showed no differences between patients and controls (P = 0.495 for BAT, P = 1.000 for BAt, P = 0.508 for Bat and P = 0.924 for bAT haplotypes, respectively). Furthermore, haplotypes were not associated with serum PTH levels or with the ratio between serum PTH and 25-hydroxyvitamin D levels. CONCLUSION: Chronic /"secondary hyperparathyroidism"/ after biliopancreatic diversion in patients with normal levels of 25-hydroxyvitamin D is not dependent on vitamin D receptor gene polymorphisms. | [
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20389122 | Factors affecting survival of patients with neurodegenerative disease. | BACKGROUND: Survival varies widely among different neurodegenerative diseases. Data on the role of the Mini Mental State Examination (MMSE) and apolipoprotein E (APOE) in survival are sparse except for Alzheimer's disease (AD). METHODS: We studied mortality of 3,581 patients in an academic clinic from 1993 to 2004. Average follow-up was 4.1 years. We studied patients with amyotrophic lateral sclerosis (ALS) (n = 174), possible AD (n = 206), probable AD (n = 1,175), Parkinson's disease (PD) (n = 661), mild cognitive impairment (MCI) (n = 357), frontotemporal dementia (FTD) (n = 94), Lewy body disease (LBD) (n = 64), and controls (n = 850). We compared patients' mortality to the US population and to controls. RESULTS: Mortality ranged from 7% for controls to 58% for ALS patients. The median survival times from initial visit for PD, FTD, probable AD, possible AD, LBD, and ALS were 8.9, 7.0, 5.9, 5.6, 5.3, and 2.7 years, respectively. Mortality rate ratios comparing each disease to controls were 39.43, 7.25, 3.70, 3.51, 2.47, 2.73, and 1.61 for ALS, FTD, LBD, PD, probable AD, possible AD, and MCI, respectively. A lower initial MMSE score was associated with higher mortality for probable AD, PD, and MCI, while APOE4 predicted mortality for PD and LBD. Non-whites had 20% lower mortality rates than whites for all dementias combined, adjusting for education. CONCLUSIONS: All neurologic diseases, including MCI, had increased mortality versus controls. A lower MMSE score and APOE4 presence predicted higher mortality for some patient groups. | Factors affecting survival of patients with /"neurodegenerative disease"/. | BACKGROUND: Survival varies widely among different /"neurodegenerative diseases"/. Data on the role of the Mini Mental State Examination (MMSE) and /"apolipoprotein E"/ (/"APOE"/) in survival are sparse except for Alzheimer's disease (AD). METHODS: We studied mortality of 3,581 patients in an academic clinic from 1993 to 2004. Average follow-up was 4.1 years. We studied patients with amyotrophic lateral sclerosis (ALS) (n = 174), possible AD (n = 206), probable AD (n = 1,175), Parkinson's disease (PD) (n = 661), mild cognitive impairment (MCI) (n = 357), frontotemporal dementia (FTD) (n = 94), Lewy body disease (LBD) (n = 64), and controls (n = 850). We compared patients' mortality to the US population and to controls. RESULTS: Mortality ranged from 7% for controls to 58% for ALS patients. The median survival times from initial visit for PD, FTD, probable AD, possible AD, LBD, and ALS were 8.9, 7.0, 5.9, 5.6, 5.3, and 2.7 years, respectively. Mortality rate ratios comparing each disease to controls were 39.43, 7.25, 3.70, 3.51, 2.47, 2.73, and 1.61 for ALS, FTD, LBD, PD, probable AD, possible AD, and MCI, respectively. A lower initial MMSE score was associated with higher mortality for probable AD, PD, and MCI, while /"APOE4"/ predicted mortality for PD and LBD. Non-whites had 20% lower mortality rates than whites for all dementias combined, adjusting for education. CONCLUSIONS: All neurologic diseases, including MCI, had increased mortality versus controls. A lower MMSE score and /"APOE4"/ presence predicted higher mortality for some patient groups. | [
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20389122 | Factors affecting survival of patients with neurodegenerative disease. | BACKGROUND: Survival varies widely among different neurodegenerative diseases. Data on the role of the Mini Mental State Examination (MMSE) and apolipoprotein E (APOE) in survival are sparse except for Alzheimer's disease (AD). METHODS: We studied mortality of 3,581 patients in an academic clinic from 1993 to 2004. Average follow-up was 4.1 years. We studied patients with amyotrophic lateral sclerosis (ALS) (n = 174), possible AD (n = 206), probable AD (n = 1,175), Parkinson's disease (PD) (n = 661), mild cognitive impairment (MCI) (n = 357), frontotemporal dementia (FTD) (n = 94), Lewy body disease (LBD) (n = 64), and controls (n = 850). We compared patients' mortality to the US population and to controls. RESULTS: Mortality ranged from 7% for controls to 58% for ALS patients. The median survival times from initial visit for PD, FTD, probable AD, possible AD, LBD, and ALS were 8.9, 7.0, 5.9, 5.6, 5.3, and 2.7 years, respectively. Mortality rate ratios comparing each disease to controls were 39.43, 7.25, 3.70, 3.51, 2.47, 2.73, and 1.61 for ALS, FTD, LBD, PD, probable AD, possible AD, and MCI, respectively. A lower initial MMSE score was associated with higher mortality for probable AD, PD, and MCI, while APOE4 predicted mortality for PD and LBD. Non-whites had 20% lower mortality rates than whites for all dementias combined, adjusting for education. CONCLUSIONS: All neurologic diseases, including MCI, had increased mortality versus controls. A lower MMSE score and APOE4 presence predicted higher mortality for some patient groups. | Factors affecting survival of patients with neurodegenerative disease. | BACKGROUND: Survival varies widely among different neurodegenerative diseases. Data on the role of the Mini Mental State Examination (MMSE) and /"apolipoprotein E"/ (/"APOE"/) in survival are sparse except for /"Alzheimer's disease"/ (/"AD"/). METHODS: We studied mortality of 3,581 patients in an academic clinic from 1993 to 2004. Average follow-up was 4.1 years. We studied patients with amyotrophic lateral sclerosis (ALS) (n = 174), possible /"AD"/ (n = 206), probable /"AD"/ (n = 1,175), Parkinson's disease (PD) (n = 661), mild cognitive impairment (MCI) (n = 357), frontotemporal dementia (FTD) (n = 94), Lewy body disease (LBD) (n = 64), and controls (n = 850). We compared patients' mortality to the US population and to controls. RESULTS: Mortality ranged from 7% for controls to 58% for ALS patients. The median survival times from initial visit for PD, FTD, probable /"AD"/, possible /"AD"/, LBD, and ALS were 8.9, 7.0, 5.9, 5.6, 5.3, and 2.7 years, respectively. Mortality rate ratios comparing each disease to controls were 39.43, 7.25, 3.70, 3.51, 2.47, 2.73, and 1.61 for ALS, FTD, LBD, PD, probable /"AD"/, possible /"AD"/, and MCI, respectively. A lower initial MMSE score was associated with higher mortality for probable /"AD"/, PD, and MCI, while /"APOE4"/ predicted mortality for PD and LBD. Non-whites had 20% lower mortality rates than whites for all dementias combined, adjusting for education. CONCLUSIONS: All neurologic diseases, including MCI, had increased mortality versus controls. A lower MMSE score and /"APOE4"/ presence predicted higher mortality for some patient groups. | [
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20393813 | Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. | Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. | Functional polymorphism in the /"interleukin-6"/ and interleukin-10 genes in patients with paranoid /"schizophrenia"/--a case-control study. | /"Schizophrenia"/ is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in /"schizophrenia"/ has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of /"interleukin (IL)-6"/ and IL-10 are risk factors for the development of paranoid /"schizophrenia"/ in case-control study. /"IL-6"/ (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid /"schizophrenia"/ and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in /"IL-6"/ and IL-10 promoter haplotypes may play an important role in determining the transcription level for /"IL-6"/ and IL-10 genes in /"schizophrenic"/ patients. The presence of allele C at position -174 of /"IL-6"/ promoter sequence may correlate with increasing risk of paranoid /"schizophrenia"/ in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid /"schizophrenia"/ in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of /"IL-6"/ promoter sequence correlates with increasing risk of paranoid /"schizophrenia"/ in the Polish population. | [
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20393813 | Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. | Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. | Functional polymorphism in the interleukin-6 and /"interleukin-10"/ genes in patients with paranoid /"schizophrenia"/--a case-control study. | /"Schizophrenia"/ is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in /"schizophrenia"/ has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and /"IL-10"/ are risk factors for the development of paranoid /"schizophrenia"/ in case-control study. IL-6 (-174G/C; rs 1800795) and /"IL-10"/ (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid /"schizophrenia"/ and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and /"IL-10"/ promoter haplotypes may play an important role in determining the transcription level for IL-6 and /"IL-10"/ genes in /"schizophrenic"/ patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid /"schizophrenia"/ in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of /"IL-10"/ promoter sequence correlates with increasing risk of paranoid /"schizophrenia"/ in the Polish population. The coexistence of genotype GG at position -1082 of /"IL-10"/ promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid /"schizophrenia"/ in the Polish population. | [
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20402821 | Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | Polymorphism of glutathione S-transferase M1 and T1 gene loci in /"COPD"/. | /"Chronic obstructive pulmonary disease"/ (/"COPD"/) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of /"COPD"/ patients and healthy controls. Genetic polymorphisms of GSTM1 and /"GSTT1"/ genes in 50 /"COPD"/ patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to /"COPD"/. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in /"COPD"/ cases when compared with controls (32.0%). The difference was not significant showing that risk of /"COPD"/ was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of /"GSTT1"/ were significantly higher in /"COPD"/ cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to /"COPD"/. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and /"GSTT1"/. It was also observed that /"COPD"/ developed in the early age and with a shorter pack-year history in Indian population. | [
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20402821 | Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | Polymorphism of /"glutathione S-transferase M1"/ and T1 gene loci in /"COPD"/. | /"Chronic obstructive pulmonary disease"/ (/"COPD"/) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of /"COPD"/ patients and healthy controls. Genetic polymorphisms of /"GSTM1"/ and GSTT1 genes in 50 /"COPD"/ patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to /"COPD"/. All subjects were males and smokers. The frequency of /"GSTM1"/ homozygous null genotype was 28.0% in /"COPD"/ cases when compared with controls (32.0%). The difference was not significant showing that risk of /"COPD"/ was not associated with the /"GSTM1"/ null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in /"COPD"/ cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to /"COPD"/. No significant differences were observed when comparisons were performed according to severity of disease and smoking for /"GSTM1"/ and GSTT1. It was also observed that /"COPD"/ developed in the early age and with a shorter pack-year history in Indian population. | [
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20402821 | Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | Polymorphism of /"glutathione S-transferase M1"/ and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and /"emphysema"/, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of /"GSTM1"/ and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of /"GSTM1"/ homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the /"GSTM1"/ null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for /"GSTM1"/ and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | [
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20402821 | Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD. | Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and /"emphysema"/, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and /"GSTT1"/ genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of /"GSTT1"/ were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and /"GSTT1"/. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population. | [
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20467232 | The polymorphism in aldehyde dehydrogenase-2 gene is associated with elevated plasma levels of high-sensitivity C-reactive protein in the early phase of myocardial infarction. | Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme of alcohol metabolism, catalyzing the conversion of aldehyde to acetic acid. The G-to-A polymorphism in exon 12 of the ALDH2 gene, which causes Glu-to-Lys substitution at codon 504, has been shown to be an independent risk factor for acute myocardial infarction (AMI). We investigated the possible role of the G-to-A polymorphism in the severity of the myocardial damage in the early phase of AMI by measuring plasma levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). A total of 226 Han Chinese patients with AMI were divided into two groups: subjects without A allele (GG, n = 144) and subjects with A allele (GA and AA, n = 82), and the blood samples were collected within 12 hours after the onset of AMI. The results displayed that high-density lipoprotein cholesterol (HDL-C) was higher in GG group than that in GA and AA group (p < 0.05). The body mass index (BMI) and the concentration of hs-CRP were lower in GG group than that in GA and AA group (p < 0.05). Multivariate logistic regression analysis showed that subjects with the A allele were at an increased risk for the high level of hs-CRP (> 3 mg/L) compared with those with GG genotype (OR = 4.908, 95% CI = 1.57 approximately 20.98). Thus, the A allele in ALDH2 gene is associated with the elevated plasma levels of hs-CRP after the onset of AMI, suggesting a higher susceptibility of the myocardium to ischemic injuries. | The polymorphism in /"aldehyde dehydrogenase-2"/ gene is associated with elevated plasma levels of high-sensitivity C-reactive protein in the early phase of /"myocardial infarction"/. | /"Aldehyde dehydrogenase-2"/ (/"ALDH2"/) is a key enzyme of alcohol metabolism, catalyzing the conversion of aldehyde to acetic acid. The G-to-A polymorphism in exon 12 of the /"ALDH2"/ gene, which causes Glu-to-Lys substitution at codon 504, has been shown to be an independent risk factor for /"acute myocardial infarction"/ (/"AMI"/). We investigated the possible role of the G-to-A polymorphism in the severity of the myocardial damage in the early phase of /"AMI"/ by measuring plasma levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). A total of 226 Han Chinese patients with /"AMI"/ were divided into two groups: subjects without A allele (GG, n = 144) and subjects with A allele (GA and AA, n = 82), and the blood samples were collected within 12 hours after the onset of /"AMI"/. The results displayed that high-density lipoprotein cholesterol (HDL-C) was higher in GG group than that in GA and AA group (p < 0.05). The body mass index (BMI) and the concentration of hs-CRP were lower in GG group than that in GA and AA group (p < 0.05). Multivariate logistic regression analysis showed that subjects with the A allele were at an increased risk for the high level of hs-CRP (> 3 mg/L) compared with those with GG genotype (OR = 4.908, 95% CI = 1.57 approximately 20.98). Thus, the A allele in /"ALDH2"/ gene is associated with the elevated plasma levels of hs-CRP after the onset of /"AMI"/, suggesting a higher susceptibility of the myocardium to ischemic injuries. | [
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} | Yes |
20467232 | The polymorphism in aldehyde dehydrogenase-2 gene is associated with elevated plasma levels of high-sensitivity C-reactive protein in the early phase of myocardial infarction. | Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme of alcohol metabolism, catalyzing the conversion of aldehyde to acetic acid. The G-to-A polymorphism in exon 12 of the ALDH2 gene, which causes Glu-to-Lys substitution at codon 504, has been shown to be an independent risk factor for acute myocardial infarction (AMI). We investigated the possible role of the G-to-A polymorphism in the severity of the myocardial damage in the early phase of AMI by measuring plasma levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). A total of 226 Han Chinese patients with AMI were divided into two groups: subjects without A allele (GG, n = 144) and subjects with A allele (GA and AA, n = 82), and the blood samples were collected within 12 hours after the onset of AMI. The results displayed that high-density lipoprotein cholesterol (HDL-C) was higher in GG group than that in GA and AA group (p < 0.05). The body mass index (BMI) and the concentration of hs-CRP were lower in GG group than that in GA and AA group (p < 0.05). Multivariate logistic regression analysis showed that subjects with the A allele were at an increased risk for the high level of hs-CRP (> 3 mg/L) compared with those with GG genotype (OR = 4.908, 95% CI = 1.57 approximately 20.98). Thus, the A allele in ALDH2 gene is associated with the elevated plasma levels of hs-CRP after the onset of AMI, suggesting a higher susceptibility of the myocardium to ischemic injuries. | The polymorphism in /"aldehyde dehydrogenase-2"/ gene is associated with elevated plasma levels of high-sensitivity C-reactive protein in the early phase of myocardial infarction. | /"Aldehyde dehydrogenase-2"/ (/"ALDH2"/) is a key enzyme of alcohol metabolism, catalyzing the conversion of aldehyde to acetic acid. The G-to-A polymorphism in exon 12 of the /"ALDH2"/ gene, which causes Glu-to-Lys substitution at codon 504, has been shown to be an independent risk factor for acute myocardial infarction (AMI). We investigated the possible role of the G-to-A polymorphism in the severity of the /"myocardial damage"/ in the early phase of AMI by measuring plasma levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). A total of 226 Han Chinese patients with AMI were divided into two groups: subjects without A allele (GG, n = 144) and subjects with A allele (GA and AA, n = 82), and the blood samples were collected within 12 hours after the onset of AMI. The results displayed that high-density lipoprotein cholesterol (HDL-C) was higher in GG group than that in GA and AA group (p < 0.05). The body mass index (BMI) and the concentration of hs-CRP were lower in GG group than that in GA and AA group (p < 0.05). Multivariate logistic regression analysis showed that subjects with the A allele were at an increased risk for the high level of hs-CRP (> 3 mg/L) compared with those with GG genotype (OR = 4.908, 95% CI = 1.57 approximately 20.98). Thus, the A allele in /"ALDH2"/ gene is associated with the elevated plasma levels of hs-CRP after the onset of AMI, suggesting a higher susceptibility of the myocardium to ischemic injuries. | [
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20483145 | Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: is it a susceptibility gene? | PURPOSE: Multiple Sclerosis (MS) is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of the brain and spinal cord. MEFV gene, which is the main factor in familial Mediterranean fever, is an intracellular regulator of inflammation. This study was designed to determine if known mutations in pyrin domain of MEFV gene are involved in MS and associated with MS morbidity. METHODS: Fifty-three patients with MS and 66 healthy subjects, who were all Turkish, were included in this study. Five pyrin gene mutations (E148Q, M680I, M694V, M694I and V726A) were detected in the patients and controls by using the PRONTO FMF Basic Kit according to the manufacturer's instructions. RESULTS: Pyrin gene mutations were found in 20 of the 53 MS patients (38%) and in seven of the 66 healthy subjects (11%). The frequency of total pyrin domain mutations was significantly higher in the MS patients than in the healthy subjects (p<0.0001). The frequencies of M694V, E148Q and V726A mutations were significantly higher in the patients than in the healthy subjects (p=0.02, p=0.013, p=0.004 respectively). The mean time to reach EDSS score 3.0 was earlier in the patients with MEFV gene mutation (p=0.02) and the relapse rate was slightly higher among the MS patients carrying MEFV gene mutation (p=0.04). CONCLUSION: The results of this study supported the hypothesis that MS patients with MEFV mutation seem to have the susceptibility to develop a more progressive disease. Moreover, these data suggest that MEFV mutations may increase the risk of MS development. | Evaluation of common mutations in the Mediterranean fever gene in /"Multiple Sclerosis"/ patients: is it a susceptibility gene? | PURPOSE: /"Multiple Sclerosis"/ (/"MS"/) is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of the brain and spinal cord. /"MEFV"/ gene, which is the main factor in familial Mediterranean fever, is an intracellular regulator of inflammation. This study was designed to determine if known mutations in pyrin domain of /"MEFV"/ gene are involved in /"MS"/ and associated with /"MS"/ morbidity. METHODS: Fifty-three patients with /"MS"/ and 66 healthy subjects, who were all Turkish, were included in this study. Five pyrin gene mutations (E148Q, M680I, M694V, M694I and V726A) were detected in the patients and controls by using the PRONTO FMF Basic Kit according to the manufacturer's instructions. RESULTS: Pyrin gene mutations were found in 20 of the 53 /"MS"/ patients (38%) and in seven of the 66 healthy subjects (11%). The frequency of total pyrin domain mutations was significantly higher in the /"MS"/ patients than in the healthy subjects (p<0.0001). The frequencies of M694V, E148Q and V726A mutations were significantly higher in the patients than in the healthy subjects (p=0.02, p=0.013, p=0.004 respectively). The mean time to reach EDSS score 3.0 was earlier in the patients with /"MEFV"/ gene mutation (p=0.02) and the relapse rate was slightly higher among the /"MS"/ patients carrying /"MEFV"/ gene mutation (p=0.04). CONCLUSION: The results of this study supported the hypothesis that /"MS"/ patients with /"MEFV"/ mutation seem to have the susceptibility to develop a more progressive disease. Moreover, these data suggest that /"MEFV"/ mutations may increase the risk of /"MS"/ development. | [
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} | Yes |
20483145 | Evaluation of common mutations in the Mediterranean fever gene in Multiple Sclerosis patients: is it a susceptibility gene? | PURPOSE: Multiple Sclerosis (MS) is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of the brain and spinal cord. MEFV gene, which is the main factor in familial Mediterranean fever, is an intracellular regulator of inflammation. This study was designed to determine if known mutations in pyrin domain of MEFV gene are involved in MS and associated with MS morbidity. METHODS: Fifty-three patients with MS and 66 healthy subjects, who were all Turkish, were included in this study. Five pyrin gene mutations (E148Q, M680I, M694V, M694I and V726A) were detected in the patients and controls by using the PRONTO FMF Basic Kit according to the manufacturer's instructions. RESULTS: Pyrin gene mutations were found in 20 of the 53 MS patients (38%) and in seven of the 66 healthy subjects (11%). The frequency of total pyrin domain mutations was significantly higher in the MS patients than in the healthy subjects (p<0.0001). The frequencies of M694V, E148Q and V726A mutations were significantly higher in the patients than in the healthy subjects (p=0.02, p=0.013, p=0.004 respectively). The mean time to reach EDSS score 3.0 was earlier in the patients with MEFV gene mutation (p=0.02) and the relapse rate was slightly higher among the MS patients carrying MEFV gene mutation (p=0.04). CONCLUSION: The results of this study supported the hypothesis that MS patients with MEFV mutation seem to have the susceptibility to develop a more progressive disease. Moreover, these data suggest that MEFV mutations may increase the risk of MS development. | Evaluation of common mutations in the Mediterranean /"fever"/ gene in Multiple Sclerosis patients: is it a susceptibility gene? | PURPOSE: Multiple Sclerosis (MS) is a disease of the central nervous system characterized by multiple areas of inflammation and demyelination in the white matter of the brain and spinal cord. /"MEFV"/ gene, which is the main factor in familial Mediterranean fever, is an intracellular regulator of inflammation. This study was designed to determine if known mutations in pyrin domain of /"MEFV"/ gene are involved in MS and associated with MS morbidity. METHODS: Fifty-three patients with MS and 66 healthy subjects, who were all Turkish, were included in this study. Five pyrin gene mutations (E148Q, M680I, M694V, M694I and V726A) were detected in the patients and controls by using the PRONTO FMF Basic Kit according to the manufacturer's instructions. RESULTS: Pyrin gene mutations were found in 20 of the 53 MS patients (38%) and in seven of the 66 healthy subjects (11%). The frequency of total pyrin domain mutations was significantly higher in the MS patients than in the healthy subjects (p<0.0001). The frequencies of M694V, E148Q and V726A mutations were significantly higher in the patients than in the healthy subjects (p=0.02, p=0.013, p=0.004 respectively). The mean time to reach EDSS score 3.0 was earlier in the patients with /"MEFV"/ gene mutation (p=0.02) and the relapse rate was slightly higher among the MS patients carrying /"MEFV"/ gene mutation (p=0.04). CONCLUSION: The results of this study supported the hypothesis that MS patients with /"MEFV"/ mutation seem to have the susceptibility to develop a more progressive disease. Moreover, these data suggest that /"MEFV"/ mutations may increase the risk of MS development. | [
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20484924 | Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and asthma. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma. | Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and /"asthma"/. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and /"IL4R"/ polymorphisms are associated with /"asthma"/ and show gene-gene interaction in /"asthma"/. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and /"IL4R"/ polymorphisms in relation to rhinitis, /"asthma"/, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by /"asthma"/; (2) 407 trios with an asthmatic proband, and (3) 118 /"asthma"/ cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical /"asthma"/. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with /"asthma"/ and serum IgE in both /"asthma"/ populations. /"IL4R"/ Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with /"asthma"/ in the /"asthma"/ case-control population. Combining risk genotypes of IL13 Arg130Gln with /"IL4R"/ Glu375Ala, and IL13 C-1111T with /"IL4R"/ Ser478Pro yielded increased risks for /"asthma"/ compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with /"asthma"/ and rhinitis without clinical /"asthma"/; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and /"IL4R"/ polymorphisms in /"asthma"/. | [
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20484924 | Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and asthma. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma. | /"Interleukin 13"/ and interleukin 4 receptor-a polymorphisms in rhinitis and /"asthma"/. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. /"IL13"/ and IL4R polymorphisms are associated with /"asthma"/ and show gene-gene interaction in /"asthma"/. Their role in rhinitis has not been extensively studied. METHODS: Association of /"IL13"/ and IL4R polymorphisms in relation to rhinitis, /"asthma"/, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by /"asthma"/; (2) 407 trios with an asthmatic proband, and (3) 118 /"asthma"/ cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: /"IL13"/ C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical /"asthma"/. /"IL13"/ Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with /"asthma"/ and serum IgE in both /"asthma"/ populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with /"asthma"/ in the /"asthma"/ case-control population. Combining risk genotypes of /"IL13"/ Arg130Gln with IL4R Glu375Ala, and /"IL13"/ C-1111T with IL4R Ser478Pro yielded increased risks for /"asthma"/ compared to their separate effects. CONCLUSION: /"IL13"/ polymorphisms were associated with /"asthma"/ and rhinitis without clinical /"asthma"/; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of /"IL13"/ and IL4R polymorphisms in /"asthma"/. | [
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20484924 | Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and asthma. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma. | Interleukin 13 and interleukin 4 receptor-a polymorphisms in /"rhinitis"/ and asthma. | BACKGROUND: Asthma and /"rhinitis"/ may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and /"IL4R"/ polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in /"rhinitis"/ has not been extensively studied. METHODS: Association of IL13 and /"IL4R"/ polymorphisms in relation to /"rhinitis"/, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with /"rhinitis"/ who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with /"rhinitis"/ and atopic phenotypes in /"rhinitis"/ trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. /"IL4R"/ Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with /"IL4R"/ Glu375Ala, and IL13 C-1111T with /"IL4R"/ Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and /"rhinitis"/ without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and /"IL4R"/ polymorphisms in asthma. | [
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20484924 | Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and asthma. | BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma. | /"Interleukin 13"/ and interleukin 4 receptor-a polymorphisms in /"rhinitis"/ and asthma. | BACKGROUND: Asthma and /"rhinitis"/ may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. /"IL13"/ and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in /"rhinitis"/ has not been extensively studied. METHODS: Association of /"IL13"/ and IL4R polymorphisms in relation to /"rhinitis"/, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with /"rhinitis"/ who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: /"IL13"/ C-1111T (rs1800925) was significantly associated with /"rhinitis"/ and atopic phenotypes in /"rhinitis"/ trios that were not affected by clinical asthma. /"IL13"/ Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of /"IL13"/ Arg130Gln with IL4R Glu375Ala, and /"IL13"/ C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: /"IL13"/ polymorphisms were associated with asthma and /"rhinitis"/ without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of /"IL13"/ and IL4R polymorphisms in asthma. | [
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20485448 | Genotype-phenotype studies in a large cohort of Armenian patients with familial Mediterranean fever suggest clinical disease with heterozygous MEFV mutations. | Familial Mediterranean fever (FMF) is an autoinflammatory disorder generally caused by recessively inherited mutations in the MEFV gene. FMF is quite prevalent in Armenian population in which majority of patients have two mutated alleles, yet in 18% of symptomatic patients just one mutation has been detected. To explain this finding, we analyzed the symptoms and genotypes of 1,299 patients, including 236 affected heterozygous patients with definite diagnosis of FMF. We selected a subset of 63 heterozygous, homozygous and asymptomatic normal individuals and completely sequenced their MEFV genes (exons) to discover any other mutations potentially missed by currently used screening method. Besides four synonymous polymorphisms in exon two and five, we found a T267I mutation in one heterozygous patient with a severe case of FMF who should have been designated as compound heterozygous, yet the other genotypes were all accurate. We used binomial probability distribution of symptoms in homozygous FMF patients to estimate the likelihood of their occurrences in heterozygous patients and demonstrated the assemblage of patients into groups with similar clinical criteria using statistical clustering. We found extremely high probabilities for the presence of FMF symptoms in heterozygous individuals and determined that symptoms were equally likely to occur in both analyzed genotypes. Therefore, our study supports the rising evidence that a single MEFV mutation could be associated with mild FMF symptoms. However, heterozygous patients presenting with severe phenotype should be further analyzed for less common second MEFV mutation using gene sequencing. | Genotype-phenotype studies in a large cohort of Armenian patients with /"familial Mediterranean fever"/ suggest clinical disease with heterozygous /"MEFV"/ mutations. | /"Familial Mediterranean fever"/ (/"FMF"/) is an autoinflammatory disorder generally caused by recessively inherited mutations in the /"MEFV"/ gene. /"FMF"/ is quite prevalent in Armenian population in which majority of patients have two mutated alleles, yet in 18% of symptomatic patients just one mutation has been detected. To explain this finding, we analyzed the symptoms and genotypes of 1,299 patients, including 236 affected heterozygous patients with definite diagnosis of /"FMF"/. We selected a subset of 63 heterozygous, homozygous and asymptomatic normal individuals and completely sequenced their /"MEFV"/ genes (exons) to discover any other mutations potentially missed by currently used screening method. Besides four synonymous polymorphisms in exon two and five, we found a T267I mutation in one heterozygous patient with a severe case of /"FMF"/ who should have been designated as compound heterozygous, yet the other genotypes were all accurate. We used binomial probability distribution of symptoms in homozygous /"FMF"/ patients to estimate the likelihood of their occurrences in heterozygous patients and demonstrated the assemblage of patients into groups with similar clinical criteria using statistical clustering. We found extremely high probabilities for the presence of /"FMF"/ symptoms in heterozygous individuals and determined that symptoms were equally likely to occur in both analyzed genotypes. Therefore, our study supports the rising evidence that a single /"MEFV"/ mutation could be associated with mild /"FMF"/ symptoms. However, heterozygous patients presenting with severe phenotype should be further analyzed for less common second /"MEFV"/ mutation using gene sequencing. | [
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20485448 | Genotype-phenotype studies in a large cohort of Armenian patients with familial Mediterranean fever suggest clinical disease with heterozygous MEFV mutations. | Familial Mediterranean fever (FMF) is an autoinflammatory disorder generally caused by recessively inherited mutations in the MEFV gene. FMF is quite prevalent in Armenian population in which majority of patients have two mutated alleles, yet in 18% of symptomatic patients just one mutation has been detected. To explain this finding, we analyzed the symptoms and genotypes of 1,299 patients, including 236 affected heterozygous patients with definite diagnosis of FMF. We selected a subset of 63 heterozygous, homozygous and asymptomatic normal individuals and completely sequenced their MEFV genes (exons) to discover any other mutations potentially missed by currently used screening method. Besides four synonymous polymorphisms in exon two and five, we found a T267I mutation in one heterozygous patient with a severe case of FMF who should have been designated as compound heterozygous, yet the other genotypes were all accurate. We used binomial probability distribution of symptoms in homozygous FMF patients to estimate the likelihood of their occurrences in heterozygous patients and demonstrated the assemblage of patients into groups with similar clinical criteria using statistical clustering. We found extremely high probabilities for the presence of FMF symptoms in heterozygous individuals and determined that symptoms were equally likely to occur in both analyzed genotypes. Therefore, our study supports the rising evidence that a single MEFV mutation could be associated with mild FMF symptoms. However, heterozygous patients presenting with severe phenotype should be further analyzed for less common second MEFV mutation using gene sequencing. | Genotype-phenotype studies in a large cohort of Armenian patients with familial Mediterranean fever suggest clinical disease with heterozygous /"MEFV"/ mutations. | Familial Mediterranean fever (FMF) is an /"autoinflammatory disorder"/ generally caused by recessively inherited mutations in the /"MEFV"/ gene. FMF is quite prevalent in Armenian population in which majority of patients have two mutated alleles, yet in 18% of symptomatic patients just one mutation has been detected. To explain this finding, we analyzed the symptoms and genotypes of 1,299 patients, including 236 affected heterozygous patients with definite diagnosis of FMF. We selected a subset of 63 heterozygous, homozygous and asymptomatic normal individuals and completely sequenced their /"MEFV"/ genes (exons) to discover any other mutations potentially missed by currently used screening method. Besides four synonymous polymorphisms in exon two and five, we found a T267I mutation in one heterozygous patient with a severe case of FMF who should have been designated as compound heterozygous, yet the other genotypes were all accurate. We used binomial probability distribution of symptoms in homozygous FMF patients to estimate the likelihood of their occurrences in heterozygous patients and demonstrated the assemblage of patients into groups with similar clinical criteria using statistical clustering. We found extremely high probabilities for the presence of FMF symptoms in heterozygous individuals and determined that symptoms were equally likely to occur in both analyzed genotypes. Therefore, our study supports the rising evidence that a single /"MEFV"/ mutation could be associated with mild FMF symptoms. However, heterozygous patients presenting with severe phenotype should be further analyzed for less common second /"MEFV"/ mutation using gene sequencing. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of HTR2C, but not /"LEP"/ or INSIG2, genes with antipsychotic-induced /"weight gain"/ in a German sample. | BACKGROUND: Drug-induced /"bodyweight gain"/ (/"BWG"/) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (/"LEP"/). PATIENTS _ METHODS: We investigated the association of HTR2C, /"LEP"/ and INSIG2 SNPs with antipsychotic-induced /"BWG"/ in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; /"LEP"/: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced /"BWG"/. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and /"LEP"/ SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced /"BWG"/. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of HTR2C, but not LEP or /"INSIG2"/, genes with antipsychotic-induced /"weight gain"/ in a German sample. | BACKGROUND: Drug-induced /"bodyweight gain"/ (/"BWG"/) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), /"insulin-induced gene 2"/ (/"INSIG2"/) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and /"INSIG2"/ SNPs with antipsychotic-induced /"BWG"/ in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; /"INSIG2"/: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced /"BWG"/. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for /"INSIG2"/ and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced /"BWG"/. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of /"HTR2C"/, but not LEP or INSIG2, genes with antipsychotic-induced /"weight gain"/ in a German sample. | BACKGROUND: Drug-induced /"bodyweight gain"/ (/"BWG"/) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (/"HTR2C"/), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of /"HTR2C"/, LEP and INSIG2 SNPs with antipsychotic-induced /"BWG"/ in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (/"HTR2C"/: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three /"HTR2C"/ SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced /"BWG"/. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal /"HTR2C"/ gene with antipsychotic-induced /"BWG"/. The proposed underlying mechanisms include decreased /"HTR2C"/ gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of /"HTR2C"/, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (/"HTR2C"/), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of /"HTR2C"/, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German /"schizophrenic"/ patients. Genotyping was performed for nine SNPs (/"HTR2C"/: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three /"HTR2C"/ SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal /"HTR2C"/ gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased /"HTR2C"/ gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of /"HTR2C"/, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (/"HTR2C"/), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of /"HTR2C"/, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German /"schizophrenic"/ patients. Genotyping was performed for nine SNPs (/"HTR2C"/: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three /"HTR2C"/ SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal /"HTR2C"/ gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased /"HTR2C"/ gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20504252 | Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (HTR2C), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of HTR2C, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German schizophrenic patients. Genotyping was performed for nine SNPs (HTR2C: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three HTR2C SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal HTR2C gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased HTR2C gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | Association of /"HTR2C"/, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. | BACKGROUND: Drug-induced bodyweight gain (BWG) is a serious concern in pharmacotherapy with second-generation antipsychotics. The interindividual variability is likely to be modulated by genetic factors. In the past, pharmacogenetic studies yielded conflicting results, and none of the identified genetic alterations exerts sufficient predictive value for this severe side effect of psychopharmacotherapy. AIM: We aimed to contribute to the replication and extension of prior association findings and investigated the genes encoding serotonin 2C receptor (/"HTR2C"/), insulin-induced gene 2 (INSIG2) and leptin (LEP). PATIENTS _ METHODS: We investigated the association of /"HTR2C"/, LEP and INSIG2 SNPs with antipsychotic-induced BWG in 128 German /"schizophrenic"/ patients. Genotyping was performed for nine SNPs (/"HTR2C"/: rs498207, rs3813928, rs6318 and rs3813929; INSIG2: rs17587100, rs10490624, rs17047764 and rs7566605; LEP: rs7799039). Association analysis included logistic regression analysis and Pearson s chi(2) tests. RESULTS: We report a significant association of three /"HTR2C"/ SNPs (rs498207, rs3813928 and rs3813929) and of the respective haplotype with antipsychotic-induced BWG. Regarding the X-chromosomal SNP rs498207, individuals with AA/A genotype gained more weight than those with GG/G genotype. The association observed with the SNP rs498207 was also significant after correcting for multiple testing (p = 0.0196). No association was found for INSIG2 and LEP SNPs. CONCLUSION: The results contribute to the accumulating evidence for an association of the X-chromosomal /"HTR2C"/ gene with antipsychotic-induced BWG. The proposed underlying mechanisms include decreased /"HTR2C"/ gene expression with reduced 5-HT-modulated activation of hypothalamic proopiomelanocortin-neurons, and inverse 5-HT(2C) agonism in the presence of D(2) receptor antagonism. | [
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20513142 | Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. | The etiology of mental retardation remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe mental retardation, epilepsy, muscular hypotonia, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the MEF2C gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered MEF2C as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe mental retardation and found two truncating and two missense de novo mutations in MEF2C, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe mental retardation accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and CDKL5 expression in vivo, and transcriptional reporter assays indicated that MEF2C mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and CDKL5. We therefore conclude that the phenotypic overlap of patients with MEF2C mutations and atypical Rett syndrome is due to the involvement of a common pathway. | Mutations in /"MEF2C"/ from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe /"mental retardation"/ and diminish MECP2 and CDKL5 expression. | The etiology of /"mental retardation"/ remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe /"mental retardation"/, epilepsy, muscular hypotonia, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the /"MEF2C"/ gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered /"MEF2C"/ as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe /"mental retardation"/ and found two truncating and two missense de novo mutations in /"MEF2C"/, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe /"mental retardation"/ accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and CDKL5 expression in vivo, and transcriptional reporter assays indicated that /"MEF2C"/ mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and CDKL5. We therefore conclude that the phenotypic overlap of patients with /"MEF2C"/ mutations and atypical Rett syndrome is due to the involvement of a common pathway. | [
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20513142 | Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. | The etiology of mental retardation remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe mental retardation, epilepsy, muscular hypotonia, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the MEF2C gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered MEF2C as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe mental retardation and found two truncating and two missense de novo mutations in MEF2C, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe mental retardation accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and CDKL5 expression in vivo, and transcriptional reporter assays indicated that MEF2C mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and CDKL5. We therefore conclude that the phenotypic overlap of patients with MEF2C mutations and atypical Rett syndrome is due to the involvement of a common pathway. | Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and /"CDKL5"/ expression. | The etiology of mental retardation remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe mental retardation, epilepsy, /"muscular hypotonia"/, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the MEF2C gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered MEF2C as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe mental retardation and found two truncating and two missense de novo mutations in MEF2C, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe mental retardation accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and /"CDKL5"/ expression in vivo, and transcriptional reporter assays indicated that MEF2C mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and /"CDKL5"/. We therefore conclude that the phenotypic overlap of patients with MEF2C mutations and atypical Rett syndrome is due to the involvement of a common pathway. | [
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20513754 | Type I interferon signaling contributes to chronic inflammation in a murine model of silicosis. | Lung disorders induced by inhaled inorganic particles such as crystalline silica are characterized by chronic inflammation and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and IRF-7 and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and IRF-7-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis. | Type I interferon signaling contributes to /"chronic inflammation"/ in a murine model of silicosis. | Lung disorders induced by inhaled inorganic particles such as crystalline silica are characterized by /"chronic inflammation"/ and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and /"IRF-7"/ and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and /"IRF-7"/-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis. | [
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20513754 | Type I interferon signaling contributes to chronic inflammation in a murine model of silicosis. | Lung disorders induced by inhaled inorganic particles such as crystalline silica are characterized by chronic inflammation and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and IRF-7 and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and IRF-7-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis. | Type I interferon signaling contributes to chronic inflammation in a murine model of silicosis. | /"Lung disorders"/ induced by inhaled inorganic particles such as crystalline silica are characterized by chronic inflammation and pulmonary fibrosis. Here, we demonstrate the importance of type I interferon (IFN) in the development of crystalline silica-induced lung inflammation in mice, revealing that viruses and inorganic particles share similar signaling pathways. We found that instillation of silica is followed by the upregulation of IFN-beta and /"IRF-7"/ and that granulocytes (GR1(+)) and macrophages/dendritic cells (CD11c(+)) are major producers of type I IFN in response to silica. Two months after silica administration, both IFNAR- and /"IRF-7"/-deficient mice produced significantly less pulmonary inflammation and chemokines (KC and CCL2) than competent mice but developed similar lung fibrosis. Our data indicate that type I IFN contributes to the chronic lung inflammation that accompanies silica exposure in mice. Type I IFN is, however, dispensable in the development of silica-induced acute lung inflammation and pulmonary fibrosis. | [
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20514303 | High transcript level of FLT3 associated with high risk of relapse in pediatric acute myeloid leukemia. | Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of acute myeloid leukemia (AML) and a mutation of FLT3 has been reported to be a risk factor, especially for pediatric patients. Recently, FLT3 expression level was implicated to have prognostic significance in adults, but little is known for childhood AML. To define the prognostic significance, transcript level of FLT3 was analyzed in 52 pediatric AML patients. The median copy number of FLT3 was 4.6x10(3) (40-5.9x10(7) copies)/1.0x10(6) GAPDH copy, and the relapse free survival of patients with high transcript level of FLT3 (>10(6) copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of FLT3 was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of FLT3 inhibitor is needed to improve outcomes. | High transcript level of /"FLT3"/ associated with high risk of relapse in /"pediatric acute myeloid leukemia"/. | Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of /"acute myeloid leukemia"/ (/"AML"/) and a mutation of /"FLT3"/ has been reported to be a risk factor, especially for pediatric patients. Recently, /"FLT3"/ expression level was implicated to have prognostic significance in adults, but little is known for childhood /"AML"/. To define the prognostic significance, transcript level of /"FLT3"/ was analyzed in 52 /"pediatric AML"/ patients. The median copy number of /"FLT3"/ was 4.6x10(3) (40-5.9x10(7) copies)/1.0x10(6) GAPDH copy, and the relapse free survival of patients with high transcript level of /"FLT3"/ (>10(6) copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of /"FLT3"/ was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of /"FLT3"/ inhibitor is needed to improve outcomes. | [
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"text_name": "pediatric acute myeloid leukemia"
} | Yes |
20514303 | High transcript level of FLT3 associated with high risk of relapse in pediatric acute myeloid leukemia. | Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of acute myeloid leukemia (AML) and a mutation of FLT3 has been reported to be a risk factor, especially for pediatric patients. Recently, FLT3 expression level was implicated to have prognostic significance in adults, but little is known for childhood AML. To define the prognostic significance, transcript level of FLT3 was analyzed in 52 pediatric AML patients. The median copy number of FLT3 was 4.6x10(3) (40-5.9x10(7) copies)/1.0x10(6) GAPDH copy, and the relapse free survival of patients with high transcript level of FLT3 (>10(6) copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of FLT3 was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of FLT3 inhibitor is needed to improve outcomes. | High transcript level of FLT3 associated with high risk of relapse in /"pediatric acute myeloid leukemia"/. | Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of /"acute myeloid leukemia"/ (/"AML"/) and a mutation of FLT3 has been reported to be a risk factor, especially for pediatric patients. Recently, FLT3 expression level was implicated to have prognostic significance in adults, but little is known for childhood /"AML"/. To define the prognostic significance, transcript level of FLT3 was analyzed in 52 /"pediatric AML"/ patients. The median copy number of FLT3 was 4.6x10(3) (40-5.9x10(7) copies)/1.0x10(6) /"GAPDH"/ copy, and the relapse free survival of patients with high transcript level of FLT3 (>10(6) copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of FLT3 was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of FLT3 inhibitor is needed to improve outcomes. | [
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},
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"entity_id": "2597",
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"text_name": "GAPDH"
} | {
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"entity_id": "D015470",
"entity_type": "Disease",
"text_name": "pediatric AML"
} | No |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, /"TMEM18"/, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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"text_name": "adult obesity"
} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and /"ETV5"/) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: /"FTO"/, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, /"KCTD15"/, NEGR1, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, /"GNPDA2"/, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, /"BDNF"/, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, /"MC4R"/, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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} | Yes |
20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of /"adult obesity"/ risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with /"adult obesity"/ risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to /"adult obesity"/. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, /"NEGR1"/, BDNF, and ETV5) were used to derive an "/"obesity"/-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The /"obesity"/-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The /"obesity"/-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to /"adult obesity"/ risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, /"BDNF"/, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: /"FTO"/, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy /"failure to thrive"/ was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy /"failure to thrive"/ (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, /"TMEM18"/, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, /"TMEM18"/, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, /"TMEM18"/, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: /"FTO"/, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy /"failure to thrive"/ was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy /"failure to thrive"/ (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: /"FTO"/, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520848 | Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | Genetic markers of adult obesity risk are associated with greater early infancy /"weight gain"/ and growth. | BACKGROUND: Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity. METHODS AND FINDINGS: Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, /"MC4R"/, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an "obesity-risk-allele score" comprising the total number of risk alleles (range: 2-15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as /"weight gain"/ between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00-0.02), but had an apparently much larger positive effect on early infancy /"weight gain"/ (0.119 SDS/allele/year; 0.023-0.216) than on subsequent childhood /"weight gain"/ (0.004 SDS/allele/year; 0.004-0.005). The obesity-risk-allele score was also positively associated with early infancy /"length gain"/ (0.158 SDS/allele/year; 0.032-0.284) and with reduced risk of early infancy failure to thrive (odds ratio = 0.92 per allele; 0.86-0.98; p = 0.009). CONCLUSIONS: The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort. | [
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20520958 | Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals. | OBJECTIVE: The relationship between variants of the leptin gene (LEP) and obesity and metabolic biomarkers was investigated in Brazilian individuals. SUBJECTS AND METHODS: One-hundred-ten obese (BMI > 30 kg/m(2)) and 100 non-obese individuals (145 women and 65 men, aged 49 +/- 14 years) were randomly selected. Plasma leptin, glycemia, serum lipid measurements and LEP -2548G>A and 3'HVR polymorphisms were analyzed. RESULTS: The LEP -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma leptin (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). LEP I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, leptin and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. LEP I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. CONCLUSIONS: LEP I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner. | Relationship between variants of the /"leptin"/ gene and /"obesity"/ and metabolic biomarkers in Brazilian individuals. | OBJECTIVE: The relationship between variants of the /"leptin"/ gene (/"LEP"/) and /"obesity"/ and metabolic biomarkers was investigated in Brazilian individuals. SUBJECTS AND METHODS: One-hundred-ten obese (BMI > 30 kg/m(2)) and 100 /"non-obese"/ individuals (145 women and 65 men, aged 49 +/- 14 years) were randomly selected. Plasma /"leptin"/, glycemia, serum lipid measurements and /"LEP"/ -2548G>A and 3'HVR polymorphisms were analyzed. RESULTS: The /"LEP"/ -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma /"leptin"/ (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). /"LEP"/ I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with /"obesity"/, and increased BMI, waist circumference, /"leptin"/ and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. /"LEP"/ I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. CONCLUSIONS: /"LEP"/ I/G combined genotypes are associated with /"obesity"/-related metabolic biomarkers and phenotype in a gender-dependent manner. | [
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20520958 | Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals. | OBJECTIVE: The relationship between variants of the leptin gene (LEP) and obesity and metabolic biomarkers was investigated in Brazilian individuals. SUBJECTS AND METHODS: One-hundred-ten obese (BMI > 30 kg/m(2)) and 100 non-obese individuals (145 women and 65 men, aged 49 +/- 14 years) were randomly selected. Plasma leptin, glycemia, serum lipid measurements and LEP -2548G>A and 3'HVR polymorphisms were analyzed. RESULTS: The LEP -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma leptin (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). LEP I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, leptin and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. LEP I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. CONCLUSIONS: LEP I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner. | Relationship between variants of the /"leptin"/ gene and obesity and metabolic biomarkers in Brazilian individuals. | OBJECTIVE: The relationship between variants of the /"leptin"/ gene (/"LEP"/) and obesity and metabolic biomarkers was investigated in Brazilian individuals. SUBJECTS AND METHODS: One-hundred-ten obese (BMI > 30 kg/m(2)) and 100 non-obese individuals (145 women and 65 men, aged 49 +/- 14 years) were randomly selected. Plasma /"leptin"/, glycemia, serum lipid measurements and /"LEP"/ -2548G>A and 3'HVR polymorphisms were analyzed. RESULTS: The /"LEP"/ -2548GG genotype was associated with a 2.2% and 2.0% increase in BMI (p = 0.009) and plasma /"leptin"/ (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8% of BMI values (p = 0.046). /"LEP"/ I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, /"leptin"/ and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. /"LEP"/ I/G combined genotypes were not associated with hypertension, hyperglycemia, /"dyslipidemia"/ and coronary artery disease. CONCLUSIONS: /"LEP"/ I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner. | [
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20522430 | Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. | BACKGROUND Mutations in SCN1A can cause genetic epilepsy with febrile seizures plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited SCN1A mutation. OBJECTIVES AND PATIENTS 19 selected families with at least one DS patient were studied to describe the mechanisms accounting for inherited SCN1A mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele specific assays. RESULTS Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04-85%. In the six remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. CONCLUSION The results indicate that mosaicism is found in at least 7% of families with DS. In the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation. | Mechanisms for variable expressivity of inherited /"SCN1A"/ mutations causing /"Dravet syndrome"/. | BACKGROUND Mutations in /"SCN1A"/ can cause genetic epilepsy with febrile seizures plus (GEFS+, inherited missense mutations) or /"Dravet syndrome"/ (/"DS"/, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of /"DS"/ patients have an inherited /"SCN1A"/ mutation. OBJECTIVES AND PATIENTS 19 selected families with at least one /"DS"/ patient were studied to describe the mechanisms accounting for inherited /"SCN1A"/ mutations in /"DS"/. The mutation identified in the /"DS"/ probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele specific assays. RESULTS Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04-85%. In the six remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including /"DS"/ as the more severe clinical picture. CONCLUSION The results indicate that mosaicism is found in at least 7% of families with /"DS"/. In the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation. | [
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20522430 | Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. | BACKGROUND Mutations in SCN1A can cause genetic epilepsy with febrile seizures plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited SCN1A mutation. OBJECTIVES AND PATIENTS 19 selected families with at least one DS patient were studied to describe the mechanisms accounting for inherited SCN1A mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele specific assays. RESULTS Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04-85%. In the six remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. CONCLUSION The results indicate that mosaicism is found in at least 7% of families with DS. In the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation. | Mechanisms for variable expressivity of inherited /"SCN1A"/ mutations causing Dravet syndrome. | BACKGROUND Mutations in /"SCN1A"/ can cause /"genetic epilepsy"/ with febrile seizures plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited /"SCN1A"/ mutation. OBJECTIVES AND PATIENTS 19 selected families with at least one DS patient were studied to describe the mechanisms accounting for inherited /"SCN1A"/ mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele specific assays. RESULTS Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04-85%. In the six remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. CONCLUSION The results indicate that mosaicism is found in at least 7% of families with DS. In the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation. | [
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20533278 | [Association of MICA gene polymorphism and serum soluble MICA level with colorectal cancer]. | OBJECTIVE: To investigate whether the major histocompatibility complex class I chain-related gene A gene (MICA) polymorphism and serum soluble MICA level were associated with the occurrence and development of colorectal cancer. METHODS: DNA samples from 117 colorectal cancer patients and 113 healthy individuals from Yangzhou in Jiangsu province were genotyped by using the polymerase chain reaction (PCR) and sequence-specific primer (SSP) method and PCR based sequencing. In addition, polymorphism at position 129 was also analyzed by PCR-SSP. Serum levels of soluble MICA were measured by a sandwich ELISA method. RESULTS: Neither the extracellular nor the transmembrane region polymorphisms of MICA gene were associated with the occurrence and the different stages of colorectal cancer. In contrast, the frequency of the methionine residue at position 129 was significantly decreased in the patient group. Soluble MICA levels in sera were increased in the late stages of colorectal cancer. CONCLUSION: Although there was no genetic susceptibility attributed to MICA gene polymorphism with regard to development of colorectal cancer, serum levels of soluble MICA may be a diagnostic marker of advanced stages. | [Association of /"MICA"/ gene polymorphism and serum soluble /"MICA"/ level with /"colorectal cancer"/]. | OBJECTIVE: To investigate whether the major histocompatibility complex class I chain-related gene A gene (/"MICA"/) polymorphism and serum soluble /"MICA"/ level were associated with the occurrence and development of /"colorectal cancer"/. METHODS: DNA samples from 117 /"colorectal cancer"/ patients and 113 healthy individuals from Yangzhou in Jiangsu province were genotyped by using the polymerase chain reaction (PCR) and sequence-specific primer (SSP) method and PCR based sequencing. In addition, polymorphism at position 129 was also analyzed by PCR-SSP. Serum levels of soluble /"MICA"/ were measured by a sandwich ELISA method. RESULTS: Neither the extracellular nor the transmembrane region polymorphisms of /"MICA"/ gene were associated with the occurrence and the different stages of /"colorectal cancer"/. In contrast, the frequency of the methionine residue at position 129 was significantly decreased in the patient group. Soluble /"MICA"/ levels in sera were increased in the late stages of /"colorectal cancer"/. CONCLUSION: Although there was no genetic susceptibility attributed to /"MICA"/ gene polymorphism with regard to development of /"colorectal cancer"/, serum levels of soluble /"MICA"/ may be a diagnostic marker of advanced stages. | [
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20543710 | Apolipoprotein E genotypes in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. | PURPOSE: Pseudoexfoliation (PEX) syndrome, an age-related, systemic, elastic microfibrillopathy, is characterized by fibrillar-granular deposits in the anterior segment of the eye. Although not representing a true amyloidosis, PEX syndrome shares some features with amyloid disorders, such as Alzheimer disease. It has been shown that amyloid-associated proteins also occur in association with PEX fibrils. Apolipoprotein E (Apo-E) is directly involved in these amyloid deposition and fibrils formation. The 4 allele of APOE gene was shown to be associated both with an increased risk for coronary heart disease and late-onset Alzheimer disease. In this study, we therefore investigated whether APOE alleles are associated with PEX syndrome and/or PEX glaucoma (PEXG) in 2 large cohorts of German and Italian origin. METHODS: The 3 common APOE alleles 2, 3, and 4 were genotyped in 661 unrelated patients (459 PEXG and 202 PEX patients) and 342 healthy individuals of German origin and furthermore in 209 unrelated patients (133 PEXG and 76 PEX patients) and 190 healthy individuals of Italian origin using TaqMan assays for allelic discrimination. A genetic association study was then performed. RESULTS: The 3 allele was found to be the most common in both populations (80% to 83%), whereas the 2 allele was the rarest (6% to 9%). No significant differences in allele and genotype frequencies between both groups were observed in either population. CONCLUSION: Our data show that APOE genotypes are not associated with PEX and PEXG in either Germans or Italians. | /"Apolipoprotein E"/ genotypes in /"pseudoexfoliation syndrome"/ and /"pseudoexfoliation glaucoma"/. | PURPOSE: Pseudoexfoliation (PEX) syndrome, an age-related, systemic, elastic microfibrillopathy, is characterized by fibrillar-granular deposits in the anterior segment of the eye. Although not representing a true amyloidosis, PEX syndrome shares some features with amyloid disorders, such as Alzheimer disease. It has been shown that amyloid-associated proteins also occur in association with PEX fibrils. /"Apolipoprotein E"/ (/"Apo-E"/) is directly involved in these amyloid deposition and fibrils formation. The 4 allele of /"APOE"/ gene was shown to be associated both with an increased risk for coronary heart disease and late-onset Alzheimer disease. In this study, we therefore investigated whether /"APOE"/ alleles are associated with PEX syndrome and/or /"PEX glaucoma"/ (/"PEXG"/) in 2 large cohorts of German and Italian origin. METHODS: The 3 common /"APOE"/ alleles 2, 3, and 4 were genotyped in 661 unrelated patients (459 /"PEXG"/ and 202 PEX patients) and 342 healthy individuals of German origin and furthermore in 209 unrelated patients (133 /"PEXG"/ and 76 PEX patients) and 190 healthy individuals of Italian origin using TaqMan assays for allelic discrimination. A genetic association study was then performed. RESULTS: The 3 allele was found to be the most common in both populations (80% to 83%), whereas the 2 allele was the rarest (6% to 9%). No significant differences in allele and genotype frequencies between both groups were observed in either population. CONCLUSION: Our data show that /"APOE"/ genotypes are not associated with PEX and /"PEXG"/ in either Germans or Italians. | [
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"end_idx": "56",
"entity_id": "D017889",
"entity_type": "Disease",
"text_name": "pseudoexfoliation syndrome"
} | Yes |
20543710 | Apolipoprotein E genotypes in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. | PURPOSE: Pseudoexfoliation (PEX) syndrome, an age-related, systemic, elastic microfibrillopathy, is characterized by fibrillar-granular deposits in the anterior segment of the eye. Although not representing a true amyloidosis, PEX syndrome shares some features with amyloid disorders, such as Alzheimer disease. It has been shown that amyloid-associated proteins also occur in association with PEX fibrils. Apolipoprotein E (Apo-E) is directly involved in these amyloid deposition and fibrils formation. The 4 allele of APOE gene was shown to be associated both with an increased risk for coronary heart disease and late-onset Alzheimer disease. In this study, we therefore investigated whether APOE alleles are associated with PEX syndrome and/or PEX glaucoma (PEXG) in 2 large cohorts of German and Italian origin. METHODS: The 3 common APOE alleles 2, 3, and 4 were genotyped in 661 unrelated patients (459 PEXG and 202 PEX patients) and 342 healthy individuals of German origin and furthermore in 209 unrelated patients (133 PEXG and 76 PEX patients) and 190 healthy individuals of Italian origin using TaqMan assays for allelic discrimination. A genetic association study was then performed. RESULTS: The 3 allele was found to be the most common in both populations (80% to 83%), whereas the 2 allele was the rarest (6% to 9%). No significant differences in allele and genotype frequencies between both groups were observed in either population. CONCLUSION: Our data show that APOE genotypes are not associated with PEX and PEXG in either Germans or Italians. | /"Apolipoprotein E"/ genotypes in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. | PURPOSE: Pseudoexfoliation (PEX) syndrome, an age-related, systemic, elastic microfibrillopathy, is characterized by fibrillar-granular deposits in the anterior segment of the eye. Although not representing a true amyloidosis, PEX syndrome shares some features with amyloid disorders, such as /"Alzheimer disease"/. It has been shown that amyloid-associated proteins also occur in association with PEX fibrils. /"Apolipoprotein E"/ (/"Apo-E"/) is directly involved in these amyloid deposition and fibrils formation. The 4 allele of /"APOE"/ gene was shown to be associated both with an increased risk for coronary heart disease and late-onset /"Alzheimer disease"/. In this study, we therefore investigated whether /"APOE"/ alleles are associated with PEX syndrome and/or PEX glaucoma (PEXG) in 2 large cohorts of German and Italian origin. METHODS: The 3 common /"APOE"/ alleles 2, 3, and 4 were genotyped in 661 unrelated patients (459 PEXG and 202 PEX patients) and 342 healthy individuals of German origin and furthermore in 209 unrelated patients (133 PEXG and 76 PEX patients) and 190 healthy individuals of Italian origin using TaqMan assays for allelic discrimination. A genetic association study was then performed. RESULTS: The 3 allele was found to be the most common in both populations (80% to 83%), whereas the 2 allele was the rarest (6% to 9%). No significant differences in allele and genotype frequencies between both groups were observed in either population. CONCLUSION: Our data show that /"APOE"/ genotypes are not associated with PEX and PEXG in either Germans or Italians. | [
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"end_idx": "735",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "Alzheimer disease"
} | No |
20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited /"thrombophilia"/ during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of /"factor V Leiden"/ (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited /"thrombophilia"/ stemming from either /"factor V Leiden"/ or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with /"factor V Leiden"/ mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with /"factor V Leiden"/ mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing /"venous TE"/. | [
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"end_idx": "888",
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"text_name": "factor V Leiden"
} | {
"begin_idx": "97",
"end_idx": "110",
"entity_id": "D019851",
"entity_type": "Disease",
"text_name": "thrombophilia"
} | Yes |
20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited /"thrombophilia"/ during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and /"prothrombin"/ (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited /"thrombophilia"/ stemming from either factor V Leiden or /"prothrombin"/ gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a /"prothrombin"/ (/"PT"/) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and /"PT"/ gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing /"venous TE"/. | [
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] | {
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} | {
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"end_idx": "110",
"entity_id": "D019851",
"entity_type": "Disease",
"text_name": "thrombophilia"
} | Yes |
20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with /"acute lymphoblastic leukemia"/ and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with /"acute lymphoblastic leukemia"/ (/"ALL"/). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with /"ALL"/ during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with /"ALL"/ is controversial. Our group investigated the use of LMWH as a prophylactic treatment for /"ALL"/ children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with /"ALL"/ treated between the years 1999 and 2008 were studied. Genetic analysis of /"factor V Leiden"/ (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either /"factor V Leiden"/ or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with /"factor V Leiden"/ mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with /"ALL"/ and PT gene mutation may have a higher risk of clotting complications in comparison to patients with /"factor V Leiden"/ mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | [
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20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with /"acute lymphoblastic leukemia"/ and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with /"acute lymphoblastic leukemia"/ (/"ALL"/). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with /"ALL"/ during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with /"ALL"/ is controversial. Our group investigated the use of LMWH as a prophylactic treatment for /"ALL"/ children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with /"ALL"/ treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and /"prothrombin"/ (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or /"prothrombin"/ gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a /"prothrombin"/ (/"PT"/) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with /"ALL"/ and /"PT"/ gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | [
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20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during /"L-asparaginase"/ treatment. | INTRODUCTION: /"Thrombotic"/ events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during /"L-asparaginase"/ treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of /"L-asparaginase"/ (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | [
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20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of /"factor V Leiden"/ (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either /"factor V Leiden"/ or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed /"thromboembolic"/ events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with /"factor V Leiden"/ mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with /"factor V Leiden"/ mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | [
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"text_name": "thromboembolic"
} | No |
20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited /"thrombophilia"/ during /"L-asparaginase"/ treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during /"L-asparaginase"/ treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of /"L-asparaginase"/ (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited /"thrombophilia"/ stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing /"venous TE"/. | [
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"entity_id": "D019851",
"entity_type": "Disease",
"text_name": "venous TE"
} | No |
20546854 | Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | Prophylactic therapy with enoxaparin in children with /"acute lymphoblastic leukemia"/ and inherited thrombophilia during /"L-asparaginase"/ treatment. | INTRODUCTION: Thrombotic events (TE) are well documented in patients with /"acute lymphoblastic leukemia"/ (/"ALL"/). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with /"ALL"/ during /"L-asparaginase"/ treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with /"ALL"/ is controversial. Our group investigated the use of LMWH as a prophylactic treatment for /"ALL"/ children with a genetic prothrombotic predisposition. METHODS: Eighty consecutive children with /"ALL"/ treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of /"L-asparaginase"/ (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation. RESULTS: Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH. CONCLUSION: It is suggested that patients with /"ALL"/ and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE. | [
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20553853 | Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 (XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that XRCC1 194Trp was associated with late-onset AD (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | Association of polymorphism of DNA repair gene /"XRCC1"/ with sporadic late-onset /"Alzheimer's disease"/ and age of onset in elderly Han Chinese. | /"Alzheimer's disease"/ (/"AD"/) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in /"AD"/. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of /"AD"/ patients. A functional polymorphism (Arg194Trp) of /"X-ray repair cross-complementing group 1"/ (/"XRCC1"/) gene may be associated with the repair efficiency of DNA damage which may have a role in /"AD"/. Therefore, /"XRCC1"/ Arg194Trp polymorphism may be a good candidate for genetic risk analysis in /"AD"/. A case-control study from Turkey found that /"XRCC1"/ 194Trp was associated with late-onset /"AD"/ (LOAD). In order to determine whether the /"XRCC1"/ gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of /"XRCC1"/ 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the /"XRCC1"/ 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the /"XRCC1"/ Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | [
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20553853 | Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 (XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that XRCC1 194Trp was associated with late-onset AD (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset /"Alzheimer's disease"/ and age of onset in elderly Han Chinese. | /"Alzheimer's disease"/ (/"AD"/) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in /"AD"/. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of /"AD"/ patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 (XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in /"AD"/. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in /"AD"/. A case-control study from Turkey found that XRCC1 194Trp was associated with late-onset /"AD"/ (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, /"Apolipoprotein"/ (/"APOE"/) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while /"APOE"/ epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by /"APOE"/ epsilon4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | [
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20553853 | Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 (XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that XRCC1 194Trp was associated with late-onset AD (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | Association of polymorphism of DNA repair gene /"XRCC1"/ with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive /"neuronal loss"/. There is evidence indicating that the increased DNA damages may contribute to /"neuronal loss"/ in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of /"X-ray repair cross-complementing group 1"/ (/"XRCC1"/) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, /"XRCC1"/ Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that /"XRCC1"/ 194Trp was associated with late-onset AD (LOAD). In order to determine whether the /"XRCC1"/ gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of /"XRCC1"/ 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the /"XRCC1"/ 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the /"XRCC1"/ Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | [
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20553853 | Association of polymorphism of DNA repair gene XRCC1 with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive neuronal loss. There is evidence indicating that the increased DNA damages may contribute to neuronal loss in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of X-ray repair cross-complementing group 1 (XRCC1) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, XRCC1 Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that XRCC1 194Trp was associated with late-onset AD (LOAD). In order to determine whether the XRCC1 gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of XRCC1 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the XRCC1 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the XRCC1 Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | Association of polymorphism of DNA repair gene /"XRCC1"/ with sporadic late-onset Alzheimer's disease and age of onset in elderly Han Chinese. | Alzheimer's disease (AD) is characterized by the presence of beta-amyloid plaques, neurofibrillary tangles and extensive /"neuronal loss"/. There is evidence indicating that the increased DNA damages may contribute to /"neuronal loss"/ in AD. Recently, it has been shown that the capacity of some types of DNA repair is impaired in the neurons of AD patients. A functional polymorphism (Arg194Trp) of /"X-ray repair cross-complementing group 1"/ (/"XRCC1"/) gene may be associated with the repair efficiency of DNA damage which may have a role in AD. Therefore, /"XRCC1"/ Arg194Trp polymorphism may be a good candidate for genetic risk analysis in AD. A case-control study from Turkey found that /"XRCC1"/ 194Trp was associated with late-onset AD (LOAD). In order to determine whether the /"XRCC1"/ gene Arg194Trp polymorphism contributes to the risk for LOAD in elderly Han Chinese, we have investigated it in 212 sporadic LOAD patients and 203 healthy controls from Chinese. No significantly increased risk of LOAD in the carriers of /"XRCC1"/ 194Trp allele (OR=1.04, 95% CI 0.70-1.52, P=0.860) was observed. As expected, Apolipoprotein (APOE) epsilon4 allele significantly increased the risk of LOAD (OR=2.95, 95% CI 1.90-4.58, P<0.001), while APOE epsilon2 allele significantly decreased the risk of LOAD (OR=0.13, 95% CI 0.08-0.24, P<0.001). After stratifying by APOE epsilon4 status, no increased LOAD risks associated with the /"XRCC1"/ 194Trp allele carriers were observed. Our findings suggest that it is unlikely that the /"XRCC1"/ Arg194Trp polymorphism plays a major role in the pathogenesis of LOAD in elderly Han Chinese and does not support the previous findings that 194Trp allele confers an increased risk for LOAD. | [
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20555002 | Genetic variants of vascular endothelial growth factor and risk for the development of endometriosis. | BACKGROUND/AIMS: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated. PATIENTS AND METHODS: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes. RESULTS: The VEGF +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 G/C polymorphisms (D': 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). CONCLUSION: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis. | Genetic variants of /"vascular endothelial growth factor"/ and risk for the development of /"endometriosis"/. | BACKGROUND/AIMS: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether /"vascular endothelial growth factor"/ (/"VEGF"/) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to /"endometriosis"/ was investigated. PATIENTS AND METHODS: Diagnosis of /"endometriosis"/ was made on the basis of laparoscopic findings. Stage of /"endometriosis"/ was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no /"endometriosis"/, 11 had mild or early-stage /"endometriosis"/ and 41 had severe /"endometriosis"/. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes. RESULTS: The /"VEGF"/ +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with /"endometriosis"/ had a higher incidence of the /"VEGF"/ +405 CC genotype compared with the controls (p=0.027). Women with /"VEGF"/ +405 CC genotype had 2.3-fold higher risk for /"endometriosis"/. /"VEGF"/ +405 GC genotype and G allele in the control group was higher than the /"endometriosis"/ group (p=0.039, p=0.027 respectively). The /"VEGF"/ -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The /"VEGF"/ -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between /"VEGF"/ -460 C/T and +405 G/C polymorphisms (D': 0.197, r(2)=0.013). We observed that the /"VEGF"/ 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). CONCLUSION: Our data suggest that the CC genotype of /"VEGF"/ +405 and 460T/405C haplotypes of /"VEGF"/ may be associated with the risk of /"endometriosis"/, but the G allele of /"VEGF"/ +405 appears to be protective against /"endometriosis"/. | [
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} | Yes |
20558149 | Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease. | The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | Complement receptor 1 polymorphisms and risk of late-onset /"Alzheimer's disease"/. | The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in /"Alzheimer's disease"/ (/"AD"/). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with /"AD"/ in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset /"AD"/ (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between /"AD"/ patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of /"APOE"/ epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. | [
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} | Yes |