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19524323 | Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort. | The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of TNMD is not associated with AD, but might modify the effect of APOE 4-allele in women. | /"Tenomodulin"/ variants, APOE and /"Alzheimer's disease"/ in a Finnish case-control cohort. | The tenomodulin gene (/"TNMD"/, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for /"Alzheimer's disease"/ (/"AD"/), since it is expressed in brain, alterations in angiogenesis have been linked to /"AD"/ and in our previous studies we have observed associations between /"TNMD"/ and phenotypes, which are related to increased risk of /"AD"/. The common sequence variation in the /"TNMD"/ was not associated with prevalence of /"AD"/ among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having /"AD"/ than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of /"TNMD"/ is not associated with /"AD"/, but might modify the effect of APOE 4-allele in women. | [
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19524323 | Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort. | The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of TNMD is not associated with AD, but might modify the effect of APOE 4-allele in women. | /"Tenomodulin"/ variants, APOE and Alzheimer's disease in a Finnish case-control cohort. | The /"tenomodulin gene"/ (/"TNMD"/MD"/, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between /"TNMD"/MD"/ and phenotypes, which are related to increased risk of AD. The common sequence variation in the /"TNMD"/MD"/ was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of /"TNMD"/MD"/ is not associated with AD, but might modify the effect of APOE 4-allele in women. | [
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19524323 | Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort. | The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of TNMD is not associated with AD, but might modify the effect of APOE 4-allele in women. | /"Tenomodulin"/ variants, APOE and Alzheimer's disease in a Finnish case-control cohort. | The /"tenomodulin gene"/ (/"TNMD"/MD"/, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between /"TNMD"/MD"/ and phenotypes, which are related to increased risk of AD. The common sequence variation in the /"TNMD"/MD"/ was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE 4-allele status was observed in women. Among the 4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of /"TNMD"/MD"/ is not associated with AD, but might modify the effect of APOE 4-allele in women. | [
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19526842 | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial hypertension in adolescents]. | Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential hypertension and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential hypertension in adolescents. | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial /"hypertension"/ in adolescents]. | Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and /"PSMA6"/ (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential /"hypertension"/ and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of /"PSMA6"/ dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and /"PSMA6"/ gene polymorphisms significance as the risk factors of essential /"hypertension"/ in adolescents. | [
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19526842 | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial hypertension in adolescents]. | Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential hypertension and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential hypertension in adolescents. | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial /"hypertension"/ in adolescents]. | Large multifunctional protease /"LMP2"/ (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential /"hypertension"/ and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in /"LMP2"/ gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the /"LMP2"/ and PSMA6 gene polymorphisms significance as the risk factors of essential /"hypertension"/ in adolescents. | [
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19526842 | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial hypertension in adolescents]. | Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential hypertension and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential hypertension in adolescents. | [Allele polymorphism of genes coding proteasome subunits is associated with an enhanced risk for arterial /"hypertension"/ in adolescents]. | Large multifunctional protease LMP2 (Arg60-->His), /"LMP7"/ (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential /"hypertension"/ and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of /"LMP7"/ gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential /"hypertension"/ in adolescents. | [
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19539307 | A case-control association study and family-based expression analysis of the bipolar disorder candidate gene PI4K2B. | Bipolar disorder, schizophrenia and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15-p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study. The candidate gene phosphatidylinositol 4-kinase type-II beta (PI4K2B) lies within one of these regions. PI4K2B is a strong functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Two approaches were undertaken to test the PI4K2B candidate gene as a susceptibility factor for psychiatric illness. First, a case-control association study, using tagging SNPs from the PI4K2B genomic region, in bipolar disorder (n=368), schizophrenia (n=386) and controls (n=458) showed association with a two-marker haplotype in schizophrenia but not bipolar disorder (rs10939038 and rs17408391, global P=0.005, permuted global P=0.039). Second, expression studies at the allele-specific mRNA and protein level using lymphoblastoid cell lines from members of the large Scottish family, which showed linkage to 4p15-p16 in bipolar disorder and recurrent major depression, showed no difference in expression differences between affected and non-affected family members. There is no evidence to suggest that PI4K2B is contributing to bipolar disorder in this family but a role for this gene in schizophrenia has not been excluded. | A case-control association study and family-based expression analysis of the /"bipolar disorder"/ candidate gene /"PI4K2B"/. | /"Bipolar disorder"/, schizophrenia and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of /"bipolar disorder"/ and recurrent major depression with markers on chromosome 4p15-p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study. The candidate gene /"phosphatidylinositol 4-kinase type-II beta"/ (/"PI4K2B"/) lies within one of these regions. /"PI4K2B"/ is a strong functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in /"bipolar disorder"/. Two approaches were undertaken to test the /"PI4K2B"/ candidate gene as a susceptibility factor for psychiatric illness. First, a case-control association study, using tagging SNPs from the /"PI4K2B"/ genomic region, in /"bipolar disorder"/ (n=368), schizophrenia (n=386) and controls (n=458) showed association with a two-marker haplotype in schizophrenia but not /"bipolar disorder"/ (rs10939038 and rs17408391, global P=0.005, permuted global P=0.039). Second, expression studies at the allele-specific mRNA and protein level using lymphoblastoid cell lines from members of the large Scottish family, which showed linkage to 4p15-p16 in /"bipolar disorder"/ and recurrent major depression, showed no difference in expression differences between affected and non-affected family members. There is no evidence to suggest that /"PI4K2B"/ is contributing to /"bipolar disorder"/ in this family but a role for this gene in schizophrenia has not been excluded. | [
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19539307 | A case-control association study and family-based expression analysis of the bipolar disorder candidate gene PI4K2B. | Bipolar disorder, schizophrenia and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15-p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study. The candidate gene phosphatidylinositol 4-kinase type-II beta (PI4K2B) lies within one of these regions. PI4K2B is a strong functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Two approaches were undertaken to test the PI4K2B candidate gene as a susceptibility factor for psychiatric illness. First, a case-control association study, using tagging SNPs from the PI4K2B genomic region, in bipolar disorder (n=368), schizophrenia (n=386) and controls (n=458) showed association with a two-marker haplotype in schizophrenia but not bipolar disorder (rs10939038 and rs17408391, global P=0.005, permuted global P=0.039). Second, expression studies at the allele-specific mRNA and protein level using lymphoblastoid cell lines from members of the large Scottish family, which showed linkage to 4p15-p16 in bipolar disorder and recurrent major depression, showed no difference in expression differences between affected and non-affected family members. There is no evidence to suggest that PI4K2B is contributing to bipolar disorder in this family but a role for this gene in schizophrenia has not been excluded. | A case-control association study and family-based expression analysis of the bipolar disorder candidate gene /"PI4K2B"/. | Bipolar disorder, schizophrenia and recurrent /"major depression"/ are complex psychiatric illnesses with a substantial, yet unknown genetic component. Linkage of bipolar disorder and recurrent /"major depression"/ with markers on chromosome 4p15-p16 has been identified in a large Scottish family and three smaller families. Analysis of haplotypes in the four chromosome 4p-linked families, identified two regions, each shared by three of the four families, which are also supported by a case-control association study. The candidate gene /"phosphatidylinositol 4-kinase type-II beta"/ (/"PI4K2B"/) lies within one of these regions. /"PI4K2B"/ is a strong functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Two approaches were undertaken to test the /"PI4K2B"/ candidate gene as a susceptibility factor for psychiatric illness. First, a case-control association study, using tagging SNPs from the /"PI4K2B"/ genomic region, in bipolar disorder (n=368), schizophrenia (n=386) and controls (n=458) showed association with a two-marker haplotype in schizophrenia but not bipolar disorder (rs10939038 and rs17408391, global P=0.005, permuted global P=0.039). Second, expression studies at the allele-specific mRNA and protein level using lymphoblastoid cell lines from members of the large Scottish family, which showed linkage to 4p15-p16 in bipolar disorder and recurrent /"major depression"/, showed no difference in expression differences between affected and non-affected family members. There is no evidence to suggest that /"PI4K2B"/ is contributing to bipolar disorder in this family but a role for this gene in schizophrenia has not been excluded. | [
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19546348 | Genetic variations in the hypoxia-inducible factor-1alpha gene and lung cancer. | Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1alphagene do not confer susceptibility to lung cancer. | Genetic variations in the /"hypoxia-inducible factor-1alpha"/ gene and /"lung cancer"/. | /"Hypoxia-inducible factor-1"/ (/"HIF-1"/), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the /"HIF-1"/alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven /"HIF-1"/alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among /"lung cancer"/ patients in the Turkish population. Genomic DNA was isolated from 141 /"lung cancer"/ cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the /"lung cancer"/ cases and controls in terms of the distribution of genotyping frequencies of seven /"HIF-1"/alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of /"lung cancer"/. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the /"HIF-1"/alphagene do not confer susceptibility to /"lung cancer"/. | [
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19546348 | Genetic variations in the hypoxia-inducible factor-1alpha gene and lung cancer. | Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1alphagene do not confer susceptibility to lung cancer. | Genetic variations in the /"hypoxia-inducible factor-1alpha"/ gene and lung cancer. | /"Hypoxia-inducible factor-1"/ (/"HIF-1"/), an important genetic component of angiogenesis, becomes stable as a response to tumor /"hypoxia"/ and facilitates tumor survival. The polymorphisms of the /"HIF-1"/alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven /"HIF-1"/alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven /"HIF-1"/alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the /"HIF-1"/alphagene do not confer susceptibility to lung cancer. | [
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19549929 | Qualification of cardiac troponin I concentration in mouse serum using isoproterenol and implementation in pharmacology studies to accelerate drug development. | Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in cTnI concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, cTnI concentration was a reliable stand-alone biomarker of cardiac injury and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to cardiotoxicity. Additional attributes, including low cost and rapid turnaround time, made cTnI concentration in serum invaluable for detecting cardiotoxicity, exploring structure-activity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery. | Qualification of /"cardiac troponin I"/ concentration in mouse serum using isoproterenol and implementation in pharmacology studies to accelerate drug development. | /"Cardiac troponin I"/ is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between /"cTnI"/ concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased /"cTnI"/ concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in /"cTnI"/ concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, /"cTnI"/ concentration was a reliable stand-alone biomarker of /"cardiac injury"/ and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to cardiotoxicity. Additional attributes, including low cost and rapid turnaround time, made /"cTnI"/ concentration in serum invaluable for detecting cardiotoxicity, exploring structure-activity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery. | [
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19549929 | Qualification of cardiac troponin I concentration in mouse serum using isoproterenol and implementation in pharmacology studies to accelerate drug development. | Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in cTnI concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, cTnI concentration was a reliable stand-alone biomarker of cardiac injury and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to cardiotoxicity. Additional attributes, including low cost and rapid turnaround time, made cTnI concentration in serum invaluable for detecting cardiotoxicity, exploring structure-activity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery. | Qualification of cardiac troponin I concentration in mouse serum using isoproterenol and implementation in pharmacology studies to accelerate drug development. | Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased /"fatty acid binding protein 3"/ concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in cTnI concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, cTnI concentration was a reliable stand-alone biomarker of cardiac injury and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to /"cardiotoxicity"/. Additional attributes, including low cost and rapid turnaround time, made cTnI concentration in serum invaluable for detecting /"cardiotoxicity"/, exploring structure-activity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery. | [
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19553609 | Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of age-related macular degeneration (AMD). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) AMD were genotyped using the assay, and the impact on AMD risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having AMD eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | Contribution of copy number variation in the regulation of complement activation locus to development of /"age-related macular degeneration"/. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (/"CFHR1"/) and determine the contribution of copy number variation (CNV) at CFHR3 and /"CFHR1"/ to the development of /"age-related macular degeneration"/ (/"AMD"/). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and /"CFHR1"/ in humans. Subjects with (n = 252) and without (n = 249) /"AMD"/ were genotyped using the assay, and the impact on /"AMD"/ risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and /"CFHR1"/ in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and /"CFHR1"/ deletion (14%), CFHR3-only deletion (0.4%), /"CFHR1"/-only deletion (1.1%), and /"CFHR1"/ duplication (0.1%). Deletion of both copies of CFHR3 and /"CFHR1"/ decreased the odds of having /"AMD"/ eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of CFHR3 and /"CFHR1"/ could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and /"CFHR1"/ protected against the development of /"AMD"/ at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | [
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"entity_id": "D008268",
"entity_type": "Disease",
"text_name": "age-related macular degeneration"
} | Yes |
19553609 | Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of age-related macular degeneration (AMD). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) AMD were genotyped using the assay, and the impact on AMD risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having AMD eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | Contribution of copy number variation in the regulation of complement activation locus to development of /"age-related macular degeneration"/. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (/"CFHR3"/) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at /"CFHR3"/ and CFHR1 to the development of /"age-related macular degeneration"/ (/"AMD"/). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of /"CFHR3"/ and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) /"AMD"/ were genotyped using the assay, and the impact on /"AMD"/ risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of /"CFHR3"/ and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both /"CFHR3"/ and CFHR1 deletion (14%), /"CFHR3"/-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of /"CFHR3"/ and CFHR1 decreased the odds of having /"AMD"/ eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of /"CFHR3"/ and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of /"CFHR3"/ and CFHR1 protected against the development of /"AMD"/ at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | [
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"text_name": "age-related macular degeneration"
} | Yes |
19553609 | Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of age-related macular degeneration (AMD). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) AMD were genotyped using the assay, and the impact on AMD risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having AMD eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | Contribution of copy number variation in the regulation of complement activation locus to development of /"age-related macular degeneration"/. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of /"age-related macular degeneration"/ (/"AMD"/). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) /"AMD"/ were genotyped using the assay, and the impact on /"AMD"/ risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having /"AMD"/ eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in /"CFH"/. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of /"AMD"/ at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | [
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"text_name": "age-related macular degeneration"
} | No |
19553609 | Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of age-related macular degeneration (AMD). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) AMD were genotyped using the assay, and the impact on AMD risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having AMD eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in CFH. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | Contribution of copy number variation in the regulation of complement activation locus to development of /"age-related macular degeneration"/. | PURPOSE: To develop an assay for determining the number of copies of the genes encoding complement factor H related 3 (CFHR3) and 1 (CFHR1) and determine the contribution of copy number variation (CNV) at CFHR3 and CFHR1 to the development of /"age-related macular degeneration"/ (/"AMD"/). METHODS: A multiplex ligation-dependent probe amplification (MLPA) assay was developed to quantify the number of copies of CFHR3 and CFHR1 in humans. Subjects with (n = 252) and without (n = 249) /"AMD"/ were genotyped using the assay, and the impact on /"AMD"/ risk was evaluated. RESULTS: The MLPA assay provided a consistent estimate of the number of copies of CFHR3 and CFHR1 in 500 of the 501 samples. Four different combinations of CNVs were observed with frequencies as follows: both CFHR3 and CFHR1 deletion (14%), CFHR3-only deletion (0.4%), CFHR1-only deletion (1.1%), and CFHR1 duplication (0.1%). Deletion of both copies of CFHR3 and CFHR1 decreased the odds of having /"AMD"/ eightfold (95% CI 2-36) and always occurred on a protective haplotype, never on the risk haplotype tagged by the Y402H risk allele in /"CFH"/. The protection conferred by deletion of CFHR3 and CFHR1 could not be distinguished from the absence of the risk haplotype. CONCLUSIONS: Both deletions and duplications of genes in the regulation of complement activation locus segregated in Caucasians. Deletion of CFHR3 and CFHR1 protected against the development of /"AMD"/ at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype. | [
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19563289 | The role of the composite interleukin-1 genotype in the association between periodontitis and acute myocardial infarction. | BACKGROUND: Recent data indicate that interleukin (IL)-1 polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at IL-1A -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and periodontitis. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci IL-1A -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between periodontitis and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | The role of the composite /"interleukin-1"/ genotype in the association between /"periodontitis"/ and acute myocardial infarction. | BACKGROUND: Recent data indicate that /"interleukin (IL)-1"/ polymorphism may influence the susceptibility to /"periodontitis"/ and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at /"IL-1A"/ -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and /"periodontitis"/. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of /"periodontitis"/ was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe /"periodontitis"/ (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci /"IL-1A"/ -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between /"periodontitis"/ and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | [
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19563289 | The role of the composite interleukin-1 genotype in the association between periodontitis and acute myocardial infarction. | BACKGROUND: Recent data indicate that interleukin (IL)-1 polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at IL-1A -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and periodontitis. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci IL-1A -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between periodontitis and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | The role of the composite interleukin-1 genotype in the association between /"periodontitis"/ and acute myocardial infarction. | BACKGROUND: Recent data indicate that interleukin (IL)-1 polymorphism may influence the susceptibility to /"periodontitis"/ and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at IL-1A -889 and /"IL-1B"/ +3954) in the association between acute myocardial infarction (AMI) and /"periodontitis"/. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of /"periodontitis"/ was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe /"periodontitis"/ (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci IL-1A -889 and /"IL-1B"/ +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between /"periodontitis"/ and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | [
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19563289 | The role of the composite interleukin-1 genotype in the association between periodontitis and acute myocardial infarction. | BACKGROUND: Recent data indicate that interleukin (IL)-1 polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at IL-1A -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and periodontitis. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci IL-1A -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between periodontitis and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | The role of the composite /"interleukin-1"/ genotype in the association between periodontitis and acute myocardial infarction. | BACKGROUND: Recent data indicate that /"interleukin (IL)-1"/ polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at /"IL-1A"/ -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and periodontitis. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical /"AL"/ >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical /"AL"/ >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci /"IL-1A"/ -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and /"AL"/ compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between periodontitis and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | [
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19563289 | The role of the composite interleukin-1 genotype in the association between periodontitis and acute myocardial infarction. | BACKGROUND: Recent data indicate that interleukin (IL)-1 polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at IL-1A -889 and IL-1B +3954) in the association between acute myocardial infarction (AMI) and periodontitis. METHODS: One hundred four white subjects (54 patients with AMI and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with AMI. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical AL >3 mm) were found in the AMI group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci IL-1A -889 and IL-1B +C3954 between patients with AMI and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with AMI had slightly increased PD and AL compared to IL-1 genotype-negative patients with AMI. CONCLUSIONS: The results confirmed an association between periodontitis and AMI but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with AMI. | The role of the composite /"interleukin-1"/ genotype in the association between periodontitis and /"acute myocardial infarction"/. | BACKGROUND: Recent data indicate that /"interleukin (IL)-1"/ polymorphism may influence the susceptibility to periodontitis and coronary heart diseases. The aim of this study was to evaluate the impact of the composite IL-1 genotype (allele 2 at /"IL-1A"/ -889 and IL-1B +3954) in the association between /"acute myocardial infarction"/ (/"AMI"/) and periodontitis. METHODS: One hundred four white subjects (54 patients with /"AMI"/ and 50 healthy controls) were studied; each received a comprehensive periodontal examination, including measurement of periodontal probing depth (PD) and clinical attachment level (CAL). The extent of periodontitis was assessed by the percentage of sites with clinical AL >3 mm. Polymorphisms in the IL-1 gene cluster were assessed using a reverse hybridization assay. RESULTS: Compared to controls, mean values for PD (4.6 mm versus 3.7 mm; P <0.0001) and CAL (5.4 mm versus 4.5 mm; P = 0.0001) were significantly increased among patients with /"AMI"/. Significantly more subjects with moderate or severe periodontitis (> or =33% of sites with clinical AL >3 mm) were found in the /"AMI"/ group compared to controls (31.5% versus 8%; P = 0.0016). These differences remained statistically significant after adjustment for smoking, age, and gender. No significant differences were observed in the allele frequencies of the gene loci /"IL-1A"/ -889 and IL-1B +C3954 between patients with /"AMI"/ and controls. Also, there was no difference in the frequency of the composite IL-1 genotype. IL-1 genotype-positive patients with /"AMI"/ had slightly increased PD and AL compared to IL-1 genotype-negative patients with /"AMI"/. CONCLUSIONS: The results confirmed an association between periodontitis and /"AMI"/ but failed to detect a modifying impact of the composite IL-1 genotype. Although the IL-1 genotype was only weakly associated with compromised periodontal health, it was not associated with /"AMI"/. | [
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19571538 | G771C Polymorphism in the MLXIPL Gene Is Associated with a Risk of Coronary Artery Disease in the Chinese: A Case-Control Study. | OBJECTIVES: Previously, a genome-wide scan has identified a nonsynonymous single nucleotide polymorphism (rs3812316, G771C, Gln241His) in the MLXIPL gene that is associated with the level of plasma triglycerides. However, no data are available on the association of this polymorphism with coronary artery disease (CAD) in the Chinese population. The aim of this study was to evaluate the association between a gene polymorphism related to triglyceride metabolism and CAD. METHODS: The genotype of the polymorphism in the MLXIPL gene was determined in 352 CAD patients and 152 CAD-free subjects. All of the participants were selected to study the MLXIPL gene rs3812316 polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: In Chinese participants, we observed that there was a significant difference in genotype between the cases and controls (p = 0.002). After allowance for potential confounders, unconditional logistic analysis revealed that the SNP was significantly related to a risk in CAD patients (adjusted OR 2.96, 95% CI 1.30-5.08; p =0.004). We also found that there was a significant association between the single nucleotide polymorphism and plasma triglyceride levels (OR 1.28, 95% CI 1.061-1.542; p < 0.05). CONCLUSION: The gene sequence variation in the MLXIPL gene may serve as a novel genetic marker for the risk of significant CAD. | G771C Polymorphism in the /"MLXIPL"/ Gene Is Associated with a Risk of /"Coronary Artery Disease"/ in the Chinese: A Case-Control Study. | OBJECTIVES: Previously, a genome-wide scan has identified a nonsynonymous single nucleotide polymorphism (rs3812316, G771C, Gln241His) in the /"MLXIPL"/ gene that is associated with the level of plasma triglycerides. However, no data are available on the association of this polymorphism with /"coronary artery disease"/ (/"CAD"/) in the Chinese population. The aim of this study was to evaluate the association between a gene polymorphism related to triglyceride metabolism and /"CAD"/. METHODS: The genotype of the polymorphism in the /"MLXIPL"/ gene was determined in 352 /"CAD"/ patients and 152 /"CAD"/-free subjects. All of the participants were selected to study the /"MLXIPL"/ gene rs3812316 polymorphism using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: In Chinese participants, we observed that there was a significant difference in genotype between the cases and controls (p = 0.002). After allowance for potential confounders, unconditional logistic analysis revealed that the SNP was significantly related to a risk in /"CAD"/ patients (adjusted OR 2.96, 95% CI 1.30-5.08; p =0.004). We also found that there was a significant association between the single nucleotide polymorphism and plasma triglyceride levels (OR 1.28, 95% CI 1.061-1.542; p < 0.05). CONCLUSION: The gene sequence variation in the /"MLXIPL"/ gene may serve as a novel genetic marker for the risk of significant /"CAD"/. | [
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19580347 | Associations between hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms and risk of developing breast cancer. | The C1772T, G1790A and C111A polymorphisms of Hypoxia-inducible factor-1alpha (HIF-1alpha) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 breast cancer patients and 275 normal and healthy women. We investigated the association between HIF-1alpha polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the breast cancer cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of breast cancer. Significant relationship was observed also between T allele and breast cancer risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing breast cancer, and presence of 1772T allele may be a useful genetic marker for tumor prognosis. | Associations between /"hypoxia-inducible factor-1alpha"/ (/"HIF-1alpha"/) gene polymorphisms and risk of developing /"breast cancer"/. | The C1772T, G1790A and C111A polymorphisms of /"Hypoxia-inducible factor-1alpha"/ (/"HIF-1alpha"/) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 /"breast cancer"/ patients and 275 normal and healthy women. We investigated the association between /"HIF-1alpha"/ polymorphisms and /"breast cancer"/ risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the /"breast cancer"/ cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of /"breast cancer"/. Significant relationship was observed also between T allele and /"breast cancer"/ risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing /"breast cancer"/, and presence of 1772T allele may be a useful genetic marker for tumor prognosis. | [
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19580347 | Associations between hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms and risk of developing breast cancer. | The C1772T, G1790A and C111A polymorphisms of Hypoxia-inducible factor-1alpha (HIF-1alpha) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 breast cancer patients and 275 normal and healthy women. We investigated the association between HIF-1alpha polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the breast cancer cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of breast cancer. Significant relationship was observed also between T allele and breast cancer risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing breast cancer, and presence of 1772T allele may be a useful genetic marker for tumor prognosis. | Associations between /"hypoxia-inducible factor-1alpha"/ (/"HIF-1alpha"/) gene polymorphisms and risk of developing breast cancer. | The C1772T, G1790A and C111A polymorphisms of /"Hypoxia-inducible factor-1alpha"/ (/"HIF-1alpha"/) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 breast cancer patients and 275 normal and healthy women. We investigated the association between /"HIF-1alpha"/ polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the breast cancer cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of breast cancer. Significant relationship was observed also between T allele and breast cancer risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, /"tumor"/ grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing breast cancer, and presence of 1772T allele may be a useful genetic marker for /"tumor"/ prognosis. | [
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19602897 | Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and HFE gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and HFE gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | Hepatic iron, serum ferritin, /"HFE"/ mutation, and /"hepatic fibrosis"/ in chronic hepatitis C. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and /"HFE"/ gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and /"HFE"/ gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of /"hepatic fibrosis"/ or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with /"hepatic fibrosis"/ either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of /"hepatic fibrosis"/, which does not support the significant role of iron in the progression of /"hepatic fibrosis"/. | [
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19602897 | Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and HFE gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and HFE gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | Hepatic iron, serum ferritin, /"HFE"/ mutation, and hepatic fibrosis in /"chronic hepatitis C"/. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and /"HFE"/ gene mutations in Korean patients with /"chronic hepatitis C"/ (/"CH-C"/). METHODS: 105 patients with /"CH-C"/ who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and /"HFE"/ gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean /"CH-C"/. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | [
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} | Yes |
19602897 | Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and HFE gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and HFE gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | Hepatic iron, serum ferritin, /"HFE"/ mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of /"hepatic iron deposition"/ and its relationship with blood iron indices, liver histology, and /"HFE"/ gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The /"hepatic iron deposition"/, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and /"HFE"/ gene mutation. RESULTS: /"Hepatic iron deposition"/ was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with /"hepatic iron deposition"/ by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: /"Hepatic iron deposition"/ was uncommon and mild in Korean CH-C. Neither /"hepatic iron deposition"/ nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | [
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19602897 | Hepatic iron, serum ferritin, HFE mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of hepatic iron deposition and its relationship with blood iron indices, liver histology, and HFE gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The hepatic iron deposition, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and HFE gene mutation. RESULTS: Hepatic iron deposition was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with hepatic iron deposition by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: Hepatic iron deposition was uncommon and mild in Korean CH-C. Neither hepatic iron deposition nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | Hepatic iron, serum ferritin, /"HFE"/ mutation, and hepatic fibrosis in chronic hepatitis C. | OBJECTIVES: We studied the status of /"hepatic iron deposition"/ and its relationship with blood iron indices, liver histology, and /"HFE"/ gene mutations in Korean patients with chronic hepatitis C (CH-C). METHODS: 105 patients with CH-C who underwent pretreatment liver biopsy were consecutively enrolled. The /"hepatic iron deposition"/, histological activity and fibrosis were assessed by appropriate pathological scoring systems, clinical data including serum iron indices, and /"HFE"/ gene mutation. RESULTS: /"Hepatic iron deposition"/ was found in 37 patients (35%), which was not significantly associated with degree of hepatic fibrosis or steatosis. The serum ferritin level was elevated in 27% of the patients and was an independent factor associated with /"hepatic iron deposition"/ by logistic regression; however, it was not significantly associated with hepatic fibrosis either. Only H63D heterozygote was found in 6 out of 48 patients (12.5%), which was not different from the prevalence of H63D mutation in the Korean population (8.5%). CONCLUSIONS: /"Hepatic iron deposition"/ was uncommon and mild in Korean CH-C. Neither /"hepatic iron deposition"/ nor serum ferritin were significantly related to the severity of hepatic fibrosis, which does not support the significant role of iron in the progression of hepatic fibrosis. | [
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19624571 | Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. | The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | Haplotypes encompassing the /"KIAA0391"/ and PSMA6 gene cluster confer a genetic link for myocardial infarction and /"coronary artery disease"/. | The role of the /"KIAA0391"/ and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the /"KIAA0391"/ and PSMA6 gene cluster in /"coronary artery disease"/ (/"CAD"/) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the /"KIAA0391"/ locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with /"CAD"/. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both /"CAD"/ and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the /"KIAA0391"/ and PSMA6 genes as a possible genetic link between /"CAD"/ and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | [
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19624571 | Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. | The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | Haplotypes encompassing the KIAA0391 and /"PSMA6"/ gene cluster confer a genetic link for /"myocardial infarction"/ and coronary artery disease. | The role of the KIAA0391 and /"PSMA6"/ genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and /"PSMA6"/ gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the /"PSMA6"/, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and /"myocardial infarction"/ (/"MI"/) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and /"PSMA6"/ genes as a possible genetic link between CAD and /"MI"/. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | [
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19624571 | Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. | The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | Haplotypes encompassing the KIAA0391 and /"PSMA6"/ gene cluster confer a genetic link for myocardial infarction and /"coronary artery disease"/. | The role of the KIAA0391 and /"PSMA6"/ genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and /"PSMA6"/ gene cluster in /"coronary artery disease"/ (/"CAD"/) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the /"PSMA6"/, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with /"CAD"/. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both /"CAD"/ and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and /"PSMA6"/ genes as a possible genetic link between /"CAD"/ and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | [
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19624571 | Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease. | The role of the KIAA0391 and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the KIAA0391 and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the KIAA0391 locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and myocardial infarction (MI) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the KIAA0391 and PSMA6 genes as a possible genetic link between CAD and MI. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | Haplotypes encompassing the /"KIAA0391"/ and PSMA6 gene cluster confer a genetic link for /"myocardial infarction"/ and coronary artery disease. | The role of the /"KIAA0391"/ and PSMA6 genes in predisposing individuals to disease is still not fully understood. We evaluated by molecular beacon-based genotyping assays the roles of five single nucleotide polymorphisms (SNPs) in the chromosomal region 14q13.2 harbouring the /"KIAA0391"/ and PSMA6 gene cluster in coronary artery disease (CAD) in the Saudi population. Two of the studied SNPs rs8008319 (denoted as 1) and rs7157492 (2), reside in the /"KIAA0391"/ locus, two others rs1048990 (3) and rs12878391 (4) are components of the PSMA6, while rs4981283 (5) resides downstream of both genes. In a study involving 1071 patients and 929 controls, none of the studied SNPs showed significant association with CAD. In contrast, two haplotypes consisting of 1A-2G-3C-4A-5A [O.R.(95% C.I.) = 1.49(0.95-2.35); p = 0.022] and 1A-2G-3G-4A-5A [2.24(0.84-5.98); p = 0.031] conferred risk for both CAD and /"myocardial infarction"/ (/"MI"/) in a five-SNP locus model, while another comprising 1A-2G-3C-4A-5G [2.24(0.84-5.98); p = 0.079] showed a borderline association. One haplotype consisting of 1T-2G-3C-4G-5A [0.79(0.59-1.05); p = 0.015] exhibited protective properties and another, 1T-2G-3C-4A-5G [0.20(0.03-139); p = 0.073], showed a similar but weaker trend. Our study identified haplotypes in the chromosomal region encompassing the /"KIAA0391"/ and PSMA6 genes as a possible genetic link between CAD and /"MI"/. These results also suggest that haplotypes may be more informative than individual SNPs in identifying risk factors for disease. | [
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19631393 | Matrix metalloproteinase-9 genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease. | Multiple sclerosis (MS) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the MMP-9 C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. | /"Matrix metalloproteinase-9"/ genotypes and haplotypes are associated with /"multiple sclerosis"/ and with the degree of disability of the disease. | /"Multiple sclerosis"/ (/"MS"/) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the /"MMP-9"/ C(-1562)T and (CA)(13-25) polymorphisms are associated with /"MS"/. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between /"MS"/ and healthy subjects, (CA)(n) genotypes and alleles were associated with /"MS"/. Moreover, the haplotypes are not associated with /"MS"/ but seem to be relevant to the clinical status of /"MS"/. Thus the (CA)(n) polymorphism may contribute to /"MS"/ susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. | [
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"text_name": "multiple sclerosis"
} | Yes |
19631393 | Matrix metalloproteinase-9 genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease. | Multiple sclerosis (MS) is an autoimmune disease causing severe neurological disability. This study was carried out in order to determine whether the MMP-9 C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. | /"Matrix metalloproteinase-9"/ genotypes and haplotypes are associated with multiple sclerosis and with the degree of disability of the disease. | Multiple sclerosis (MS) is an autoimmune disease causing severe /"neurological disability"/. This study was carried out in order to determine whether the /"MMP-9"/ C(-1562)T and (CA)(13-25) polymorphisms are associated with MS. A total of 165 patients (92 whites/73 mulattos) and 191 controls (96 whites/95 mulattos) were enrolled in the study. While no difference in C(-1562)T polymorphism was observed between MS and healthy subjects, (CA)(n) genotypes and alleles were associated with MS. Moreover, the haplotypes are not associated with MS but seem to be relevant to the clinical status of MS. Thus the (CA)(n) polymorphism may contribute to MS susceptibility, but C(-1562)T and (CA)(n) haplotypes may modulate disease severity. | [
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"text_name": "neurological disability"
} | No |
19638460 | Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. | PURPOSE: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS. EXPERIMENTAL DESIGN: We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles. RESULTS: The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the CYP2C19*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021). CONCLUSION: Our data show that the 5-AZA/VPA combination is active and safe in patients with MDS with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy. | Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk /"myelodysplastic syndromes"/. | PURPOSE: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of /"myelodysplastic syndromes"/ (/"MDS"/). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk /"MDS"/. EXPERIMENTAL DESIGN: We enrolled 62 patients with /"MDS"/ (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles. RESULTS: The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the /"CYP2C19"/*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021). CONCLUSION: Our data show that the 5-AZA/VPA combination is active and safe in patients with /"MDS"/ with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy. | [
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} | Yes |
19638460 | Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. | PURPOSE: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS. EXPERIMENTAL DESIGN: We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles. RESULTS: The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the CYP2C19*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021). CONCLUSION: Our data show that the 5-AZA/VPA combination is active and safe in patients with MDS with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy. | Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. | PURPOSE: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS. EXPERIMENTAL DESIGN: We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and /"chronic myelomanocytic leukemia"/ (/"CMML"/), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 microg/mL, then 5-AZA was added s.c. at 75 mg/m(2) for 7 days in eight monthly cycles. RESULTS: The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulative incidence of progression. Of 26 patients who completed eight cycles, 30.7% obtained complete or partial remission, 15.4% had a major hematologic improvement, whereas 38.5% showed stable disease. Drug-related toxicity was mild. Favorable prognostic factors for survival were IPSS Intermediate-2 and plasma VPA of > or =50 microg/mL (log rank = 0.013 and 0.007, respectively). Analysis of polymorphisms important for the metabolism of the drugs used in the trial showed that carriers of the /"CYP2C19"/*2 variant of cytochrome P450 required higher VPA doses to achieve the target VPA plasma concentration of 50 microg/mL on day 1 of 5-AZA treatment (P = 0.0021). CONCLUSION: Our data show that the 5-AZA/VPA combination is active and safe in patients with MDS with a poor prognosis. Achievement of VPA therapeutic levels may indeed increase 5-AZA efficacy. | [
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19642078 | Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients. | OBJECTIVES: Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (SLCO1B1). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in RA. METHODS: A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS: Almost 80% of RA patients had one or more risk factor (range 1-5) for the development of statin-induced myopathy. Of the 74 RA patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. CONCLUSIONS: RA patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients. | Prevalence of risk factors for statin-induced myopathy in /"rheumatoid arthritis"/ patients. | OBJECTIVES: Statins are widely prescribed in patients with /"rheumatoid arthritis"/ (/"RA"/). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (/"SLCO1B1"/). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in /"RA"/. METHODS: A total of 396 /"RA"/ patients and 438 non-/"RA"/ controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS: Almost 80% of /"RA"/ patients had one or more risk factor (range 1-5) for the development of statin-induced myopathy. Of the 74 /"RA"/ patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between /"RA"/ patients and controls. CONCLUSIONS: /"RA"/ patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of /"RA"/. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among /"RA"/ patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients. | [
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19642078 | Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients. | OBJECTIVES: Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced myopathy. Several factors increase the risk of developing statin-induced myopathy, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (SLCO1B1). We aimed to identify the frequency of risk factors for statin-induced myopathy and establish whether the rs4149056 genotype is more prevalent in RA. METHODS: A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS: Almost 80% of RA patients had one or more risk factor (range 1-5) for the development of statin-induced myopathy. Of the 74 RA patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. CONCLUSIONS: RA patients harbour multiple risk factors for statin-induced myopathy. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced myopathy were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record myopathy risk factors in these patients. | Prevalence of risk factors for statin-induced /"myopathy"/ in rheumatoid arthritis patients. | OBJECTIVES: Statins are widely prescribed in patients with rheumatoid arthritis (RA). Although statins offer overwhelming cardiovascular benefits, their use can be associated with the development of a statin-induced /"myopathy"/. Several factors increase the risk of developing statin-induced /"myopathy"/, including the single nucleotide polymorphism (SNP) rs4149056, located within the gene encoding solute carrier organic anion transporter (/"SLCO1B1"/). We aimed to identify the frequency of risk factors for statin-induced /"myopathy"/ and establish whether the rs4149056 genotype is more prevalent in RA. METHODS: A total of 396 RA patients and 438 non-RA controls were studied. DNA samples were obtained from all patients. The SNP rs4149056 was identified using real-time polymerase chain reaction and melting curve analysis. Genotypic and allelic frequencies were calculated using the chi-squared test. RESULTS: Almost 80% of RA patients had one or more risk factor (range 1-5) for the development of statin-induced /"myopathy"/. Of the 74 RA patients treated with statins, 90% had one or more (range 1-4) risk factors. No differences in genotype or allelic frequencies were observed between RA patients and controls. CONCLUSIONS: RA patients harbour multiple risk factors for statin-induced /"myopathy"/. However, the frequency of the rs4149056 genotypes does not differ according to the presence of RA. Despite this, no cases of statin-induced /"myopathy"/ were observed in this cohort over a period of four years of follow-up. Thus, we conclude that statin use among RA patients is probably safe, but large-scale prospective studies are needed to confirm this. In the meantime, it may be good practice systematically to consider and record /"myopathy"/ risk factors in these patients. | [
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"text_name": "myopathy"
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"text_name": "myopathy"
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"text_name": "myopathy"
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"text_name": "myopathy"
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}
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"text_name": "SLCO1B1"
} | {
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"entity_id": "D009135",
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"text_name": "myopathy"
} | No |
19643966 | Association of the lumican gene functional 3'-UTR polymorphism with high myopia. | PURPOSE: The lumican gene (LUM) encodes a major extracellular component of the fibrous mammalian sclera. Alteration in the expression levels of extracellular matrix components may influence scleral shape, which in turn could affect visual acuity. Single-nucleotide polymorphisms (SNPs) in the LUM gene were determined in an investigation of whether LUM gene polymorphisms correlate with high myopia. METHODS: Sequences spanning all three exons, intron-exon boundaries, and promoter regions were determined in 50 normal individuals. Five SNPs were identified, one of which was found to be a newly identified polymorphism. Genomic DNA was prepared from peripheral blood obtained from 201 patients with high myopia and 86 control subjects. Genotypes of the SNPs -1554 T/C (rs3759223), -628 A/-(rs17018757), -59 CC/-(rs3832846), c.601 T/C (rs17853500), and the novel SNP c.1567 C>T were determined by polymerase chain reaction. RESULTS: Of the five SNPs, one showed a significant difference between patients and control subjects (c.1567 C>T, P = 0.0016). Haplotype analysis revealed a significantly higher presence of polymorphisms in patients with myopia (P < 0.0001). Moreover, the c.1567 T polymorphism was determined to have lower reporter gene activity than that of c.1567 C. CONCLUSIONS: These observations suggest that LUM gene polymorphisms contribute to the development of high myopia. | Association of the /"lumican"/ gene functional 3'-UTR polymorphism with /"high myopia"/. | PURPOSE: The /"lumican"/ gene (/"LUM"/) encodes a major extracellular component of the fibrous mammalian sclera. Alteration in the expression levels of extracellular matrix components may influence scleral shape, which in turn could affect visual acuity. Single-nucleotide polymorphisms (SNPs) in the /"LUM"/ gene were determined in an investigation of whether /"LUM"/ gene polymorphisms correlate with /"high myopia"/. METHODS: Sequences spanning all three exons, intron-exon boundaries, and promoter regions were determined in 50 normal individuals. Five SNPs were identified, one of which was found to be a newly identified polymorphism. Genomic DNA was prepared from peripheral blood obtained from 201 patients with /"high myopia"/ and 86 control subjects. Genotypes of the SNPs -1554 T/C (rs3759223), -628 A/-(rs17018757), -59 CC/-(rs3832846), c.601 T/C (rs17853500), and the novel SNP c.1567 C>T were determined by polymerase chain reaction. RESULTS: Of the five SNPs, one showed a significant difference between patients and control subjects (c.1567 C>T, P = 0.0016). Haplotype analysis revealed a significantly higher presence of polymorphisms in patients with /"myopia"/ (P < 0.0001). Moreover, the c.1567 T polymorphism was determined to have lower reporter gene activity than that of c.1567 C. CONCLUSIONS: These observations suggest that /"LUM"/ gene polymorphisms contribute to the development of /"high myopia"/. | [
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19648156 | Genetic variation in RYR1 and malignant hyperthermia phenotypes. | BACKGROUND: Malignant hyperthermia (MH) is associated, in the majority of cases, with mutations in RYR1, the gene encoding the skeletal muscle ryanodine receptor. Our primary aim was to assess whether different RYR1 variants are associated with quantitative differences in MH phenotype. METHODS: The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive RYR1 genotype-phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 RYR1 variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and RYR1 genotype. RESULTS: We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical MH response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific RYR1 variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001). CONCLUSIONS: The MH phenotype differs significantly with different RYR1 variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia. | Genetic variation in /"RYR1"/ and /"Malignant hyperthermia"/ phenotypes. | BACKGROUND: /"Malignant hyperthermia"/ (/"MH"/) is associated, in the majority of cases, with mutations in /"RYR1"/, the gene encoding the /"skeletal muscle ryanodine receptor"/. Our primary aim was to assess whether different /"RYR1"/ variants are associated with quantitative differences in /"MH"/ phenotype. METHODS: The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for /"MH"/. We then undertook the most extensive /"RYR1"/ genotype-phenotype correlation in /"MH"/ to date using 504 individuals from 204 /"MH"/ families and 23 /"RYR1"/ variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and /"RYR1"/ genotype. RESULTS: We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical /"MH"/ response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific /"RYR1"/ variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001). CONCLUSIONS: The /"MH"/ phenotype differs significantly with different /"RYR1"/ variants. Variants leading to more severe /"MH"/ phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between /"RYR1"/ variants may explain the variability in clinical penetrance of /"MH"/ during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia. | [
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19648156 | Genetic variation in RYR1 and malignant hyperthermia phenotypes. | BACKGROUND: Malignant hyperthermia (MH) is associated, in the majority of cases, with mutations in RYR1, the gene encoding the skeletal muscle ryanodine receptor. Our primary aim was to assess whether different RYR1 variants are associated with quantitative differences in MH phenotype. METHODS: The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive RYR1 genotype-phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 RYR1 variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and RYR1 genotype. RESULTS: We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical MH response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific RYR1 variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001). CONCLUSIONS: The MH phenotype differs significantly with different RYR1 variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia. | Genetic variation in /"RYR1"/ and malignant hyperthermia phenotypes. | BACKGROUND: Malignant hyperthermia (MH) is associated, in the majority of cases, with mutations in /"RYR1"/, the gene encoding the /"skeletal muscle ryanodine receptor"/. Our primary aim was to assess whether different /"RYR1"/ variants are associated with quantitative differences in MH phenotype. METHODS: The degree of in vitro pharmacological /"muscle contracture"/ response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive /"RYR1"/ genotype-phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 /"RYR1"/ variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and /"RYR1"/ genotype. RESULTS: We report a novel correlation between the degree of in vitro pharmacological /"muscle contracture"/ responses and the onset time of the clinical MH response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific /"RYR1"/ variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001). CONCLUSIONS: The MH phenotype differs significantly with different /"RYR1"/ variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between /"RYR1"/ variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia. | [
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19673907 | MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women. | Data on the association of the MTHFR 677C > T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA. | /"MTHFR"/ 677C->T and ACE D/I polymorphisms and /"migraine"/ attack frequency in women. | Data on the association of the /"MTHFR"/ 677C > T and ACE D/I polymorphisms with /"migraine"/ severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-/"migraine"/ association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The /"MTHFR"/ 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA. | [
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19673907 | MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women. | Data on the association of the MTHFR 677C > T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA. | MTHFR 677C->T and /"ACE"/ D/I polymorphisms and /"migraine"/ attack frequency in women. | Data on the association of the MTHFR 677C > T and /"ACE"/ D/I polymorphisms with /"migraine"/ severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-/"migraine"/ association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the /"ACE"/ D/I polymorphism with attack frequency for MA or MoA. | [
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19673907 | MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women. | Data on the association of the MTHFR 677C > T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA. | /"MTHFR"/ 677C->T and ACE D/I polymorphisms and migraine attack frequency in women. | Data on the association of the /"MTHFR"/ 677C > T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. /"Migraine, aura status"/ and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported /"migraine with aura"/ (/"MA"/) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The /"MTHFR"/ 677TT genotype was associated with a reduced risk for /"MA"/, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for /"MA"/ or MoA. | [
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19673907 | MTHFR 677C->T and ACE D/I polymorphisms and migraine attack frequency in women. | Data on the association of the MTHFR 677C > T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA. | MTHFR 677C->T and /"ACE"/ D/I polymorphisms and migraine attack frequency in women. | Data on the association of the MTHFR 677C > T and /"ACE"/ D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 >= weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 /"migraine without aura"/ (/"MoA"/) (attack frequency: 85 >= weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the /"ACE"/ D/I polymorphism with attack frequency for MA or /"MoA"/. | [
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19687159 | Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study. | AIMS: The interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors. METHODS AND RESULTS: TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between IL-18 genotype and hypertension impacting on the risk of SCD due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, hypertension was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78-7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39-29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with IL-18 genotype affecting the expression of IL-18 (P = 0.030) mRNA and interferon-gamma mRNA (P = 0.004). CONCLUSION: Hypertension interacts with IL-18 gene promoter -137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis. | /"Interleukin 18"/ gene promoter polymorphism: a link between /"hypertension"/ and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study. | AIMS: The /"interleukin 18"/ (/"IL-18"/) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic /"IL-18"/. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors. METHODS AND RESULTS: TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between /"IL-18"/ genotype and /"hypertension"/ impacting on the risk of SCD due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, /"hypertension"/ was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78-7.91, P < 0.001] and /"hypertension"/ also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39-29.33, P < 0.001). Among C allele carriers, /"hypertension"/ was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, /"hypertension"/ also interacted significantly with /"IL-18"/ genotype affecting the expression of /"IL-18"/ (P = 0.030) mRNA and interferon-gamma mRNA (P = 0.004). CONCLUSION: /"Hypertension"/ interacts with /"IL-18"/ gene promoter -137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis. | [
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19687159 | Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study. | AIMS: The interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors. METHODS AND RESULTS: TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between IL-18 genotype and hypertension impacting on the risk of SCD due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, hypertension was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78-7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39-29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with IL-18 genotype affecting the expression of IL-18 (P = 0.030) mRNA and interferon-gamma mRNA (P = 0.004). CONCLUSION: Hypertension interacts with IL-18 gene promoter -137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis. | /"Interleukin 18"/ gene promoter polymorphism: a link between hypertension and pre-hospital /"sudden cardiac death"/: the Helsinki Sudden Death Study. | AIMS: The /"interleukin 18"/ (/"IL-18"/) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic /"IL-18"/. The C allele of this polymorphism is associated with a lower risk of /"sudden cardiac death"/ (/"SCD"/). We examined the process by which this polymorphism alters the risk of /"SCD"/ and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors. METHODS AND RESULTS: TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between /"IL-18"/ genotype and hypertension impacting on the risk of /"SCD"/ due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, hypertension was a major risk factor for /"SCD"/ due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78-7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39-29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related /"SCD"/ or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with /"IL-18"/ genotype affecting the expression of /"IL-18"/ (P = 0.030) mRNA and interferon-gamma mRNA (P = 0.004). CONCLUSION: Hypertension interacts with /"IL-18"/ gene promoter -137 G/C polymorphism, affecting the risk of /"SCD"/ and the development of coronary atherosclerosis. | [
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19698145 | Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. | BACKGROUND: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. | Replication by the Epistasis Project of the interaction between the genes for IL-6 and /"IL-10"/ in the risk of /"Alzheimer's disease"/. | BACKGROUND: Chronic inflammation is a characteristic of /"Alzheimer's disease"/ (/"AD"/). An interaction associated with the risk of /"AD"/ has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, /"interleukin-10"/ (/"IL-10"/, gene: /"IL10"/). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 /"AD"/ research groups, contributing DNA samples from 1,757 cases of /"AD"/ and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x /"IL10"/ rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and /"IL-10"/ in some elderly people, due in part to genetic variations in the two genes, contributes to the development of /"AD"/. Thus, inflammation facilitates the onset of /"sporadic AD"/. | [
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19698145 | Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. | BACKGROUND: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. | Replication by the Epistasis Project of the interaction between the genes for /"IL-6"/ and IL-10 in the risk of /"Alzheimer's disease"/. | BACKGROUND: Chronic inflammation is a characteristic of /"Alzheimer's disease"/ (/"AD"/). An interaction associated with the risk of /"AD"/ has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, /"interleukin-6"/ (/"IL-6"/, gene: /"IL6"/), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 /"AD"/ research groups, contributing DNA samples from 1,757 cases of /"AD"/ and 6,295 controls. RESULTS: We replicated the interaction. For /"IL6"/ rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both /"IL-6"/ and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of /"AD"/. Thus, inflammation facilitates the onset of /"sporadic AD"/. | [
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} | Yes |
19698145 | Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. | BACKGROUND: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. | Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of /"Alzheimer's disease"/. | BACKGROUND: Chronic inflammation is a characteristic of /"Alzheimer's disease"/ (/"AD"/). An interaction associated with the risk of /"AD"/ has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 /"AD"/ research groups, contributing DNA samples from 1,757 cases of /"AD"/ and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and /"apolipoprotein E epsilon4"/ (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of /"AD"/. Thus, inflammation facilitates the onset of /"sporadic AD"/. | [
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"entity_type": "Disease",
"text_name": "AD"
} | No |
19698145 | Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. | BACKGROUND: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. RESULTS: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. | Replication by the Epistasis Project of the interaction between the genes for /"IL-6"/ and IL-10 in the risk of Alzheimer's disease. | BACKGROUND: /"Chronic inflammation"/ is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, /"interleukin-6"/ (/"IL-6"/, gene: /"IL6"/), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). METHODS: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. RESULTS: We replicated the interaction. For /"IL6"/ rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. CONCLUSION: We suggest that dysregulation of both /"IL-6"/ and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. | [
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"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "Chronic inflammation"
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19700865 | Association of matrix metalloproteinase-2 gene promoter polymorphism with myocardial infarction susceptibility in a Mexican population. | Association of /"matrix metalloproteinase-2"/ gene promoter polymorphism with /"myocardial infarction"/ susceptibility in a Mexican population. | [
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"text_name": "myocardial infarction"
} | Yes |
||
19710694 | The purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene associated with essential hypertension in Japanese men. | P2RY2 has an important function in the regulation of blood pressure by activating adenosine triphosphate (ATP). The aim of this study was to investigate the association between the human P2RY2 gene and essential hypertension (EH) through a haplotype-based case-control study that included two gender groups. The 273 EH patients and 255 age-matched controls were genotyped for five single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936 and rs10898909). Data were analysed for men and women separately and then as a combined total group. For the total and the men only groups, the genotype distribution of the T allele of rs4944831 and the recessive model (GG vs TG+TT) of rs4944831 differed significantly between the EH patients and controls (P=0.028 and 0.019; P=0.009 and 0.008, respectively). Logistic regression showed that for the total and men groups, the TG+TT genotype of rs4944831 was more prevalent in EH patients than in the controls (P=0.026 and 0.011, respectively). For men, the overall distribution of the haplotype (SNP2-SNP4-SNP5) was significantly different between the EH patients and the controls (P=0.006). As compared with controls, the frequency of the T-A-G haplotype was significantly higher, whereas the T-C-G haplotype was significantly lower for the EH patients (P=0.001 and 0.014, respectively). In conclusion, the present results indicate that rs4944831 and the T-A-G haplotype of the human P2RY2 gene might be genetic markers for EH in Japanese men. | The /"purinergic receptor P2Y, G-protein coupled, 2"/ (/"P2RY2"/) gene associated with essential /"hypertension"/ in Japanese men. | /"P2RY2"/ has an important function in the regulation of blood pressure by activating adenosine triphosphate (ATP). The aim of this study was to investigate the association between the human /"P2RY2"/ gene and essential /"hypertension"/ (EH) through a haplotype-based case-control study that included two gender groups. The 273 EH patients and 255 age-matched controls were genotyped for five single-nucleotide polymorphisms (SNPs) of the human /"P2RY2"/ gene (rs4944831, rs1783596, rs4944832, rs4382936 and rs10898909). Data were analysed for men and women separately and then as a combined total group. For the total and the men only groups, the genotype distribution of the T allele of rs4944831 and the recessive model (GG vs TG+TT) of rs4944831 differed significantly between the EH patients and controls (P=0.028 and 0.019; P=0.009 and 0.008, respectively). Logistic regression showed that for the total and men groups, the TG+TT genotype of rs4944831 was more prevalent in EH patients than in the controls (P=0.026 and 0.011, respectively). For men, the overall distribution of the haplotype (SNP2-SNP4-SNP5) was significantly different between the EH patients and the controls (P=0.006). As compared with controls, the frequency of the T-A-G haplotype was significantly higher, whereas the T-C-G haplotype was significantly lower for the EH patients (P=0.001 and 0.014, respectively). In conclusion, the present results indicate that rs4944831 and the T-A-G haplotype of the human /"P2RY2"/ gene might be genetic markers for EH in Japanese men. | [
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19715891 | Influence of mannose-binding lectin gene polymorphisms on the invasiveness of cytomegalovirus disease after solid organ transplantation. | BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune system that binds the surface of pathogens, activating the complement pathway and acting as opsonin. Certain single-nucleotide polymorphisms of MBL2 are associated with a decrease in the circulating levels of MBL. Our aim was to evaluate the influence of MBL2 polymorphisms in the invasiveness of Cytomegalovirus (CMV) disease after solid organ transplantation. METHODS: We include those solid organ transplant recipients who developed CMV disease posttransplant from 2000 to 2006. MBL2 genotyping was performed by sequencing of exon 1 (wild-type allele A and variants B, C, and D) and promoter regions (alleles H and L, X and Y, and P and Q). In the case of liver transplantation, donor MBL2 genotypes were analyzed. Associations were calculated by the chi-square test and binary logistic regression. RESULTS: We included 45 transplant recipients with CMV disease (22 renal, 7 simultaneous kidney-pancreas, 11 liver, and 5 heart), of whom 10 (22%) had invasive CMV disease. No differences were found regarding HH (versus HL or LL), YY and YX (versus XX) and QQ (versus QP and PP) haplotypes with invasive CMV disease (P = 1.000 for all 3 comparisons). Patients with an exon 1 wild-type (AA) haplotype had 36% invasive CMV disease in comparison with 9% of patients with A/O or O/O haplotypes (P = .035). Binary logistic regression analysis showed that patients with exon 1 AA haplotype had an independent risk of developing invasive CMV disease (odds ratio, 6.0; 95% confidence interval, 1.1-32.5). CONCLUSIONS: Our results suggest that exon 1 wild-type genotypes are associated with a higher risk of invasive CMV disease after solid organ transplantation. | Influence of /"mannose-binding lectin"/ gene polymorphisms on the invasiveness of /"cytomegalovirus disease"/ after solid organ transplantation. | BACKGROUND: /"Mannose-binding lectin"/ (/"MBL"/) is a component of the innate immune system that binds the surface of pathogens, activating the complement pathway and acting as opsonin. Certain single-nucleotide polymorphisms of /"MBL2"/ are associated with a decrease in the circulating levels of /"MBL"/. Our aim was to evaluate the influence of /"MBL2"/ polymorphisms in the invasiveness of /"Cytomegalovirus (CMV) disease"/ after solid organ transplantation. METHODS: We include those solid organ transplant recipients who developed /"CMV disease"/ posttransplant from 2000 to 2006. /"MBL2"/ genotyping was performed by sequencing of exon 1 (wild-type allele A and variants B, C, and D) and promoter regions (alleles H and L, X and Y, and P and Q). In the case of liver transplantation, donor /"MBL2"/ genotypes were analyzed. Associations were calculated by the chi-square test and binary logistic regression. RESULTS: We included 45 transplant recipients with /"CMV disease"/ (22 renal, 7 simultaneous kidney-pancreas, 11 liver, and 5 heart), of whom 10 (22%) had invasive /"CMV disease"/. No differences were found regarding HH (versus HL or LL), YY and YX (versus XX) and QQ (versus QP and PP) haplotypes with invasive /"CMV disease"/ (P = 1.000 for all 3 comparisons). Patients with an exon 1 wild-type (AA) haplotype had 36% invasive /"CMV disease"/ in comparison with 9% of patients with A/O or O/O haplotypes (P = .035). Binary logistic regression analysis showed that patients with exon 1 AA haplotype had an independent risk of developing invasive /"CMV disease"/ (odds ratio, 6.0; 95% confidence interval, 1.1-32.5). CONCLUSIONS: Our results suggest that exon 1 wild-type genotypes are associated with a higher risk of invasive /"CMV disease"/ after solid organ transplantation. | [
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19723304 | Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population. | BACKGROUND: Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with ulcerative colitis patients. Detection of polymorphism in NOD1 gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of NOD1 gene in context to Indian population. METHODS: A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of NOD1 gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's chi2 test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12. RESULTS: We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of NOD1 gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg2+binding sites. No significant association was observed within different sub phenotypes. CONCLUSION: We propose that the location of mutations in the Exon 6 spanning the ATP and Mg2+ binding site of NBD in NOD1 gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility. | Frequency of single nucleotide polymorphisms in /"NOD1"/ gene of /"ulcerative colitis"/ patients: a case-control study in the Indian population. | BACKGROUND: Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding /"Nod1"/ protein still has not been well documented for its association with /"ulcerative colitis"/ patients. Detection of polymorphism in /"NOD1"/ gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of /"NOD1"/ gene in context to Indian population. METHODS: A total of 95 patients with /"ulcerative colitis"/ and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of /"NOD1"/ gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's chi2 test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12. RESULTS: We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of /"NOD1"/ gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg2+binding sites. No significant association was observed within different sub phenotypes. CONCLUSION: We propose that the location of mutations in the Exon 6 spanning the ATP and Mg2+ binding site of NBD in /"NOD1"/ gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility. | [
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19723304 | Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population. | BACKGROUND: Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with ulcerative colitis patients. Detection of polymorphism in NOD1 gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of NOD1 gene in context to Indian population. METHODS: A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of NOD1 gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's chi2 test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12. RESULTS: We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of NOD1 gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg2+binding sites. No significant association was observed within different sub phenotypes. CONCLUSION: We propose that the location of mutations in the Exon 6 spanning the ATP and Mg2+ binding site of NBD in NOD1 gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility. | Frequency of single nucleotide polymorphisms in /"NOD1"/ gene of ulcerative colitis patients: a case-control study in the Indian population. | BACKGROUND: Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to /"IBD"/. The most significant finding in the /"IBD"/ research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding /"Nod1"/ protein still has not been well documented for its association with ulcerative colitis patients. Detection of polymorphism in /"NOD1"/ gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of /"NOD1"/ gene in context to Indian population. METHODS: A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of /"NOD1"/ gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's chi2 test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12. RESULTS: We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of /"NOD1"/ gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg2+binding sites. No significant association was observed within different sub phenotypes. CONCLUSION: We propose that the location of mutations in the Exon 6 spanning the ATP and Mg2+ binding site of NBD in /"NOD1"/ gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility. | [
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19753311 | Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia. | PURPOSE: Numerous studies, including those using animal models of myopia development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to myopia development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between high myopia and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1). METHODS: The participants comprised of a high myopia group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1rs11823728), S2 (CHRM1rs544978), S3 (CHRM1rs2186410), and S4 (CHRM1rs542269). RESULTS: There was a significant difference in the distribution of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of high myopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). CONCLUSIONS: Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co-operative association with high myopia. | Muscarinic acetylcholine receptor 1 gene polymorphisms associated with /"high myopia"/. | PURPOSE: Numerous studies, including those using animal models of /"myopia"/ development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to /"myopia"/ development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between /"high myopia"/ and polymorphisms within the muscarinic acetylcholine receptors 1 gene (/"CHRM1"/). METHODS: The participants comprised of a /"high myopia"/ group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (/"CHRM1"/rs11823728), S2 (/"CHRM1"/rs544978), S3 (/"CHRM1"/rs2186410), and S4 (/"CHRM1"/rs542269). RESULTS: There was a significant difference in the distribution of S2 and S4 between the /"high myopia"/ and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 /"CHRM1"/ as all being significant in the development of /"high myopia"/. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). CONCLUSIONS: Our results suggest that the S2 and S4 polymorphisms of /"CHRM1"/ are associated with susceptibility for developing /"high myopia"/. S1, S2, and S4 /"CHRM1"/ had a co-operative association with /"high myopia"/. | [
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19753311 | Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia. | PURPOSE: Numerous studies, including those using animal models of myopia development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to myopia development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between high myopia and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1). METHODS: The participants comprised of a high myopia group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1rs11823728), S2 (CHRM1rs544978), S3 (CHRM1rs2186410), and S4 (CHRM1rs542269). RESULTS: There was a significant difference in the distribution of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of high myopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). CONCLUSIONS: Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co-operative association with high myopia. | Muscarinic acetylcholine receptor 1 gene polymorphisms associated with /"high myopia"/. | PURPOSE: Numerous studies, including those using animal models of /"myopia"/ development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to /"myopia"/ development. Among all of the muscarinic acetylcholine receptors (mAChRs), /"mAChR 1"/ (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between /"high myopia"/ and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1). METHODS: The participants comprised of a /"high myopia"/ group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1rs11823728), S2 (CHRM1rs544978), S3 (CHRM1rs2186410), and S4 (CHRM1rs542269). RESULTS: There was a significant difference in the distribution of S2 and S4 between the /"high myopia"/ and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of /"high myopia"/. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). CONCLUSIONS: Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing /"high myopia"/. S1, S2, and S4 CHRM1 had a co-operative association with /"high myopia"/. | [
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1976809 | Lack of gene deletion for complement C4A deficiency in Japanese patients with systemic lupus erythematosus. | The frequency of C4A gene deletion was studied in Japanese patients with systemic lupus erythematosus (SLE) and was compared with healthy controls. DNA preparations were extracted from peripheral blood leukocytes from 59 patients with SLE and from 166 healthy persons, and digested by restriction enzymes. They were hybridized with C4 complementary DNA by the Southern blotting method and the deletion of C4A gene was judged from restriction fragment length polymorphism. At the same time phenotypic C4A deficiency (C4AQ0) was measured. Our results showed that the frequency of phenotypic C4A deficiency was 44.1% in Japanese patients with SLE and this value was comparable with that (43.2%) in Caucasian patients. On the other hand the deletion of C4A gene was not found in Japanese patients with SLE (0%), or in healthy controls (0.6%). Our results indicate that C4AQ0 may contribute to the pathogenesis of SLE beyond the ethnical differences but Japanese patients with SLE have a different genetic background from Caucasian patients with the C4A gene deleted. | Lack of gene deletion for complement C4A deficiency in Japanese patients with /"systemic lupus erythematosus"/. | The frequency of /"C4A"/ gene deletion was studied in Japanese patients with /"systemic lupus erythematosus"/ (/"SLE"/) and was compared with healthy controls. DNA preparations were extracted from peripheral blood leukocytes from 59 patients with /"SLE"/ and from 166 healthy persons, and digested by restriction enzymes. They were hybridized with C4 complementary DNA by the Southern blotting method and the deletion of /"C4A"/ gene was judged from restriction fragment length polymorphism. At the same time phenotypic /"C4A"/ deficiency (C4AQ0) was measured. Our results showed that the frequency of phenotypic /"C4A"/ deficiency was 44.1% in Japanese patients with /"SLE"/ and this value was comparable with that (43.2%) in Caucasian patients. On the other hand the deletion of /"C4A"/ gene was not found in Japanese patients with /"SLE"/ (0%), or in healthy controls (0.6%). Our results indicate that C4AQ0 may contribute to the pathogenesis of /"SLE"/ beyond the ethnical differences but Japanese patients with /"SLE"/ have a different genetic background from Caucasian patients with the /"C4A"/ gene deleted. | [
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1976809 | Lack of gene deletion for complement C4A deficiency in Japanese patients with systemic lupus erythematosus. | The frequency of C4A gene deletion was studied in Japanese patients with systemic lupus erythematosus (SLE) and was compared with healthy controls. DNA preparations were extracted from peripheral blood leukocytes from 59 patients with SLE and from 166 healthy persons, and digested by restriction enzymes. They were hybridized with C4 complementary DNA by the Southern blotting method and the deletion of C4A gene was judged from restriction fragment length polymorphism. At the same time phenotypic C4A deficiency (C4AQ0) was measured. Our results showed that the frequency of phenotypic C4A deficiency was 44.1% in Japanese patients with SLE and this value was comparable with that (43.2%) in Caucasian patients. On the other hand the deletion of C4A gene was not found in Japanese patients with SLE (0%), or in healthy controls (0.6%). Our results indicate that C4AQ0 may contribute to the pathogenesis of SLE beyond the ethnical differences but Japanese patients with SLE have a different genetic background from Caucasian patients with the C4A gene deleted. | Lack of gene deletion for /"complement C4A deficiency"/ in Japanese patients with systemic lupus erythematosus. | The frequency of /"C4A"/ gene deletion was studied in Japanese patients with systemic lupus erythematosus (SLE) and was compared with healthy controls. DNA preparations were extracted from peripheral blood leukocytes from 59 patients with SLE and from 166 healthy persons, and digested by restriction enzymes. They were hybridized with C4 complementary DNA by the Southern blotting method and the deletion of /"C4A"/ gene was judged from restriction fragment length polymorphism. At the same time phenotypic /"C4A"/ deficiency (C4AQ0) was measured. Our results showed that the frequency of phenotypic /"C4A"/ deficiency was 44.1% in Japanese patients with SLE and this value was comparable with that (43.2%) in Caucasian patients. On the other hand the deletion of /"C4A"/ gene was not found in Japanese patients with SLE (0%), or in healthy controls (0.6%). Our results indicate that C4AQ0 may contribute to the pathogenesis of SLE beyond the ethnical differences but Japanese patients with SLE have a different genetic background from Caucasian patients with the /"C4A"/ gene deleted. | [
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19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of /"RPS14"/, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in /"RPS14"/, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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} | Yes |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in /"RPS24"/, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, /"RPS24"/, RPL5, RPL11, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in /"RPS24"/. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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} | Yes |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and /"RPL35A"/ described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and /"RPL35A"/ in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or /"RPL35A"/. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with /"RPL5"/ and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (/"RPL5"/, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, /"RPL5"/, RPL11, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in /"RPL5"/ or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with /"RPL5"/ and RPL11 mutations. A close association was evident between /"RPL5"/ mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with /"RPL5"/ and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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} | Yes |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, /"RPS16"/, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, /"RPS16"/, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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},
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} | Yes |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and /"RPL11"/ mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, /"RPL11"/), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, /"RPL11"/, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or /"RPL11"/, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and /"RPL11"/ mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and /"RPL11"/ mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and /"RPL11"/ in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and /"RPL11"/ mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients /"display various malformations"/. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, /"RPL11"/), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, /"RPL11"/, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or /"RPL11"/, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic /"malformations"/ in patients with RPL5 and /"RPL11"/ mutations. A close association was evident between RPL5 mutations and craniofacial /"malformations"/, and between hand /"malformations"/ and /"RPL11"/ mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and /"RPL11"/ in patients with Diamond-Blackfan anemia with /"malformations"/. | [
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19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | /"Diamond-Blackfan anemia"/: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: /"Diamond-Blackfan anemia"/ is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the /"RPS19"/ gene, encoding the /"ribosomal protein S19"/, are the main known cause of /"Diamond-Blackfan anemia"/ and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that /"Diamond-Blackfan anemia"/ is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with /"Diamond-Blackfan anemia"/ who were negative for /"RPS19"/ mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of /"Diamond-Blackfan anemia"/ in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with /"Diamond-Blackfan anemia"/ with malformations. | [
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} | No |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with /"RPL5"/ and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients /"display various malformations"/. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (/"RPL5"/, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, /"RPL5"/, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in /"RPL5"/ or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic /"malformations"/ in patients with /"RPL5"/ and RPL11 mutations. A close association was evident between /"RPL5"/ mutations and craniofacial /"malformations"/, and between hand /"malformations"/ and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with /"RPL5"/ and RPL11 in patients with Diamond-Blackfan anemia with /"malformations"/. | [
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} | No |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and /"RPL11"/ mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients /"display various malformations"/. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, /"RPL11"/), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, /"RPL11"/, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or /"RPL11"/, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic /"malformations"/ in patients with RPL5 and /"RPL11"/ mutations. A close association was evident between RPL5 mutations and craniofacial /"malformations"/, and between hand /"malformations"/ and /"RPL11"/ mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and /"RPL11"/ in patients with Diamond-Blackfan anemia with /"malformations"/. | [
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"text_name": "malformations"
} | No |
19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with /"RPL5"/ and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients /"display various malformations"/. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (/"RPL5"/, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, /"RPL5"/, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in /"RPL5"/ or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic /"malformations"/ in patients with /"RPL5"/ and RPL11 mutations. A close association was evident between /"RPL5"/ mutations and craniofacial /"malformations"/, and between hand /"malformations"/ and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with /"RPL5"/ and RPL11 in patients with Diamond-Blackfan anemia with /"malformations"/. | [
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19773262 | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. Anemia is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, RPS16, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, RPS16, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations. | BACKGROUND: Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. About 40% of patients display various malformations. /"Anemia"/ is corrected by steroid treatment in more than 50% of cases; non-responders need chronic transfusions or stem cell transplantation. Defects in the RPS19 gene, encoding the ribosomal protein S19, are the main known cause of Diamond-Blackfan anemia and account for more than 25% of cases. Mutations in RPS24, RPS17, and RPL35A described in a minority of patients show that Diamond-Blackfan anemia is a disorder of ribosome biogenesis. Two new genes (RPL5, RPL11), encoding for ribosomal proteins of the large subunit, have been reported to be involved in a considerable percentage of patients. DESIGN AND METHODS: In this genotype-phenotype analysis we screened the coding sequence and intron-exon boundaries of RPS14, /"RPS16"/, RPS24, RPL5, RPL11, and RPL35A in 92 Italian patients with Diamond-Blackfan anemia who were negative for RPS19 mutations. RESULTS: About 20% of the patients screened had mutations in RPL5 or RPL11, and only 1.6% in RPS24. All but three mutations that we report here are new mutations. No mutations were found in RPS14, /"RPS16"/, or RPL35A. Remarkably, we observed a higher percentage of somatic malformations in patients with RPL5 and RPL11 mutations. A close association was evident between RPL5 mutations and craniofacial malformations, and between hand malformations and RPL11 mutations. CONCLUSIONS: Mutations in four ribosomal proteins account for around 50% of all cases of Diamond-Blackfan anemia in Italian patients. Genotype-phenotype data suggest that mutation screening should begin with RPL5 and RPL11 in patients with Diamond-Blackfan anemia with malformations. | [
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19774492 | A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population. | Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392-1.986, P = 2.03 x 10(-8)]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population. | A single-nucleotide polymorphism of the /"TNFAIP3"/ gene is associated with /"systemic lupus erythematosus"/ in Chinese Han population. | /"Systemic lupus erythematosus"/ (/"SLE"/) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of /"SLE"/ is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for /"SLE"/ including /"TNFAIP3"/. In order to examine whether /"TNFAIP3"/ is associated with /"SLE"/ in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with /"SLE"/ in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and /"SLE"/ of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392-1.986, P = 2.03 x 10(-8)]. Interestingly, rs2230926 of /"TNFAIP3"/ was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the /"TNFAIP3"/ might be a common genetic factor for /"SLE"/ within different populations in terms of Chinese Han and European population. | [
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"text_name": "systemic lupus erythematosus"
} | Yes |
19774492 | A single-nucleotide polymorphism of the TNFAIP3 gene is associated with systemic lupus erythematosus in Chinese Han population. | Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392-1.986, P = 2.03 x 10(-8)]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population. | A single-nucleotide polymorphism of the /"TNFAIP3"/ gene is associated with systemic lupus erythematosus in Chinese Han population. | Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have found many novel susceptibility genes for SLE including /"TNFAIP3"/. In order to examine whether /"TNFAIP3"/ is associated with SLE in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system. Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval (CI): 1.392-1.986, P = 2.03 x 10(-8)]. Interestingly, rs2230926 of /"TNFAIP3"/ was also associated with /"arthritis"/, ANA and some other subphenotypes of the disease. Our findings suggest that SNP rs2230926 in the /"TNFAIP3"/ might be a common genetic factor for SLE within different populations in terms of Chinese Han and European population. | [
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"entity_type": "Gene",
"text_name": "TNFAIP3"
},
{
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"end_idx": "1088",
"entity_id": "7128",
"entity_type": "Gene",
"text_name": "TNFAIP3"
}
] | {
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"entity_id": "7128",
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"text_name": "TNFAIP3"
} | {
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"end_idx": "983",
"entity_id": "D001168",
"entity_type": "Disease",
"text_name": "arthritis"
} | No |
19800393 | Identification of four novel potentially Parkinson's disease associated LRRK2 variations among Iranian patients. | The results of mutation screening of 24 exons of LRRK2 in 60 Iranian Parkinson's Disease patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low. | Identification of four novel potentially /"Parkinson's disease"/ associated /"LRRK2"/ variations among Iranian patients. | The results of mutation screening of 24 exons of /"LRRK2"/ in 60 Iranian /"Parkinson's Disease"/ patients are presented. The Iranian cohort represents a novel population and was notably young (average age at onset of disease: 36.0 years). Fifty sequence variations were found, seventeen of which are novel. Variations considered possibly associated with disease were screened in available family members, 145 additional patients and 220 control individuals. It was surmised that four novel sequence variations (IVS49+178A>G, p.R1725Q, p.Q1823K, and p.D2175H) may be associated with PD status, albeit they may be very rare non-disease associated variations. The four variations were all observed in the heterozygous state in early onset cases. If one or more of the variations do indeed contribute to disease status, their penetrance is expected to be low. | [
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"text_name": "Parkinson's disease"
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"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
} | Yes |
1980685 | Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia. | An apolipoprotein A-I gene promoter polymorphism, due to an adenine (A) to guanine (G) transition 78 base pairs upstream from the transcription initiation site, was studied by amplification of the corresponding region of the apoA-I gene, DNA sequencing, and allele-specific oligonucleotide hybridization. The frequency of the polymorphism was studied on female and male individuals classified into three groups according to the high density lipoprotein (HDL) cholesterol concentration. The allelic frequencies for the A polymorphism were 0.10, 0.14, 0.27 in women and 0.08, 0.17, 0.14 in men in the lowest, in the intermediate (between 10th and 90th percentile), and the highest decile of HDL cholesterol levels, respectively. Statistical analysis showed a significant difference of allelic frequencies between the highest and the lowest deciles (P less than 0.006) and between the highest and the intermediate deciles of HDL cholesterol in women (P less than 0.04) but not in men. As the sequences surrounding the polymorphism are known to be involved in transcription modulation, it is possible that the A-G transition polymorphism may have an influence on apoA-I synthesis and, in consequence, on the HDL cholesterol levels in women. | Human /"apolipoprotein A-I"/ gene promoter polymorphism: association with /"hyperalphalipoproteinemia"/. | An /"apolipoprotein A-I"/ gene promoter polymorphism, due to an adenine (A) to guanine (G) transition 78 base pairs upstream from the transcription initiation site, was studied by amplification of the corresponding region of the /"apoA-I"/ gene, DNA sequencing, and allele-specific oligonucleotide hybridization. The frequency of the polymorphism was studied on female and male individuals classified into three groups according to the high density lipoprotein (HDL) cholesterol concentration. The allelic frequencies for the A polymorphism were 0.10, 0.14, 0.27 in women and 0.08, 0.17, 0.14 in men in the lowest, in the intermediate (between 10th and 90th percentile), and the highest decile of HDL cholesterol levels, respectively. Statistical analysis showed a significant difference of allelic frequencies between the highest and the lowest deciles (P less than 0.006) and between the highest and the intermediate deciles of HDL cholesterol in women (P less than 0.04) but not in men. As the sequences surrounding the polymorphism are known to be involved in transcription modulation, it is possible that the A-G transition polymorphism may have an influence on /"apoA-I"/ synthesis and, in consequence, on the HDL cholesterol levels in women. | [
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"text_name": "hyperalphalipoproteinemia"
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"entity_id": "C564591",
"entity_type": "Disease",
"text_name": "hyperalphalipoproteinemia"
} | Yes |
19811440 | TLR4 and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and TLR4 variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of periodontitis patients carrying TLR4 variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | /"TLR4"/ and IL-18 gene variants in /"chronic periodontitis"/: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the /"Toll-like receptor 4"/ gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to /"chronic periodontitis"/. 108 /"chronic periodontitis"/ patients and 76 controls were genotyped for c.896A>G/1196C>T (/"TLR4"/ gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with /"TLR4"/ c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and /"TLR4"/ variants have an effect on the susceptibility to /"chronic periodontitis"/. Considering the low number of periodontitis patients carrying /"TLR4"/ variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | [
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} | {
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"entity_id": "D055113",
"entity_type": "Disease",
"text_name": "chronic periodontitis"
} | Yes |
19811440 | TLR4 and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and TLR4 variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of periodontitis patients carrying TLR4 variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | TLR4 and /"IL-18"/ gene variants in /"chronic periodontitis"/: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the /"interleukin-18"/ gene are associated with the susceptibility to /"chronic periodontitis"/. 108 /"chronic periodontitis"/ patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (/"IL-18"/ promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that /"IL-18"/ and TLR4 variants have an effect on the susceptibility to /"chronic periodontitis"/. Considering the low number of periodontitis patients carrying TLR4 variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | [
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"entity_id": "D055113",
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} | Yes |
19811440 | TLR4 and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and TLR4 variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of periodontitis patients carrying TLR4 variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | TLR4 and /"IL-18"/ gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the /"interleukin-18"/ gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (/"IL-18"/ promoter). There were no significant differences in genotype and allele distributions between the study groups. /"Periodontitis"/ severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and /"periodontitis"/ (OR = 1.98, 95% CI 0.61-6.39). The results did not show that /"IL-18"/ and TLR4 variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of /"periodontitis"/ patients carrying TLR4 variants (11%), a comparison of the /"periodontitis"/ severity depending on the genotype has to be interpreted cautiously. | [
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19811440 | TLR4 and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the Toll-like receptor 4 gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (TLR4 gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. Periodontitis severity in patients with TLR4 c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and periodontitis (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and TLR4 variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of periodontitis patients carrying TLR4 variants (11%), a comparison of the periodontitis severity depending on the genotype has to be interpreted cautiously. | /"TLR4"/ and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. | The aim of the study was to assess whether genotypes in the /"Toll-like receptor 4"/ gene and in the promoter of the interleukin-18 gene are associated with the susceptibility to chronic periodontitis. 108 chronic periodontitis patients and 76 controls were genotyped for c.896A>G/1196C>T (/"TLR4"/ gene) and for c.-368G>C/ c.-838C>A (IL-18 promoter). There were no significant differences in genotype and allele distributions between the study groups. /"Periodontitis"/ severity in patients with /"TLR4"/ c.896AG/1196CT genotype was significantly higher than wildtype carriers. The percentage of teeth with clinical attachment loss > or = 5 mm was 77.3% and 58.8%, respectively (p < or = 0.006, t-test). All subjects were further classified into carriers and non-carriers of at least one variant of each gene. A logistic regression analysis adjusted for gender, smoking, and age showed no association between gene variant carrier status and /"periodontitis"/ (OR = 1.98, 95% CI 0.61-6.39). The results did not show that IL-18 and /"TLR4"/ variants have an effect on the susceptibility to chronic periodontitis. Considering the low number of /"periodontitis"/ patients carrying /"TLR4"/ variants (11%), a comparison of the /"periodontitis"/ severity depending on the genotype has to be interpreted cautiously. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), /"insulin"/ gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the /"insulin"/-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and /"ETS1"/. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (/"ETS1"/) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the /"ETS1"/ gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, /"THY1"/, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, /"Thy-1"/ (/"THY1"/), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. /"THY1"/ and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, THY1, /"CD3D"/ and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), /"T3-D"/ (/"CD3D"/), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and /"CD3D"/ genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, THY1, /"CD3D"/ and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), /"T3-D"/ (/"CD3D"/), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and /"CD3D"/ genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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1982251 | Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | Non-HLA genetic factors and /"insulin dependent diabetes mellitus"/ in the Japanese: TCRA, TCRB and TCRG, INS, THY1, /"CD3D"/ and ETS1. | Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), /"T3-D"/ (/"CD3D"/), and c-ets proto oncogene (ETS1) were investigated among 56 unrelated patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, A1 and more rarely A2 alleles were found, but with no significant frequencies. THY1 and /"CD3D"/ genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETS1 gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p less than 0.03) was found. However, this significant association disappeared when the correct p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations. | [
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19842025 | Association of interleukin-8 gene polymorphisms and haplotypes with oral lichen planus in a Chinese population. | Interleukin-8 (IL-8), a CXC chemokine with multiple biological functions, plays an important role in the pathogenesis of oral lichen planus (OLP). The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of IL-8 gene with OLP in a Chinese population. Four SNPs of the IL-8 gene at positions -845 T/C (rs2227532), -738 T/A, -251 A/T (rs4073) and +781 C/T (rs2227306) were analyzed in 109 patients with OLP and 101 normal controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data revealed that the -251 AA genotype and -251 A allele frequency was significantly lower in the erosive OLP (eOLP) group than in the control group (P = 0.012 and P = 0.031, respectively). Haplotype analysis revealed that the -251 A/+781 C haplotype frequency was lower in the eOLP group than in the control group (P = 0.029) while the -251 T/+781 C haplotype frequency was higher in the eOLP patients than in the healthy controls (P = 0.028). The study suggests that the IL-8 polymorphisms may be associated with the severity of OLP in this Chinese cohort. | Association of /"interleukin-8"/ gene polymorphisms and haplotypes with /"oral lichen planus"/ in a Chinese population. | /"Interleukin-8"/ (/"IL-8"/), a CXC chemokine with multiple biological functions, plays an important role in the pathogenesis of /"oral lichen planus"/ (/"OLP"/). The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of /"IL-8"/ gene with /"OLP"/ in a Chinese population. Four SNPs of the /"IL-8"/ gene at positions -845 T/C (rs2227532), -738 T/A, -251 A/T (rs4073) and +781 C/T (rs2227306) were analyzed in 109 patients with /"OLP"/ and 101 normal controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data revealed that the -251 AA genotype and -251 A allele frequency was significantly lower in the erosive /"OLP"/ (eOLP) group than in the control group (P = 0.012 and P = 0.031, respectively). Haplotype analysis revealed that the -251 A/+781 C haplotype frequency was lower in the eOLP group than in the control group (P = 0.029) while the -251 T/+781 C haplotype frequency was higher in the eOLP patients than in the healthy controls (P = 0.028). The study suggests that the /"IL-8"/ polymorphisms may be associated with the severity of /"OLP"/ in this Chinese cohort. | [
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19846968 | Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population. | BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy. | Association between /"XRCC1"/ polymorphisms and /"head and neck cancer"/ in a Hungarian population. | BACKGROUND: /"Head and neck cancer"/ is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the /"XRCC1"/ gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of /"XRCC1"/ on the clinical outcome of /"head and neck cancer"/. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different /"XRCC1"/ 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy. | [
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"entity_id": "D006258",
"entity_type": "Disease",
"text_name": "head and neck cancer"
} | Yes |
19846968 | Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population. | BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy. | Association between /"XRCC1"/ polymorphisms and head and neck cancer in a Hungarian population. | BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this /"cancer"/ has increased by 387% in the last thirty-two years. Because of the important role of the /"XRCC1"/ gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of /"XRCC1"/ on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched /"cancer"/-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different /"XRCC1"/ 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy. | [
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"text_name": "cancer"
} | No |
19874431 | Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis. | BACKGROUND: Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD). OBJECTIVE: In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals. RESULTS: We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co-morbidity. CONCLUSION: Our data confirm and extend the knowledge of the influence of FLG mutations in AD. | Analysis of four prevalent /"filaggrin"/ mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with /"atopic dermatitis"/. | BACKGROUND: Recently, mutations in the /"filaggrin"/ gene (/"FLG"/) have been shown to be a major predisposing factor for /"atopic dermatitis"/ (/"AD"/). OBJECTIVE: In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German /"AD"/ patients and in 402 control individuals. RESULTS: We found a strong association of the /"FLG"/ mutations with /"AD"/. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in /"AD"/ patients with concomitant asthma compared with those without this co-morbidity. CONCLUSION: Our data confirm and extend the knowledge of the influence of /"FLG"/ mutations in /"AD"/. | [
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} | Yes |
19874431 | Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis. | BACKGROUND: Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD). OBJECTIVE: In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals. RESULTS: We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co-morbidity. CONCLUSION: Our data confirm and extend the knowledge of the influence of FLG mutations in AD. | Analysis of four prevalent /"filaggrin"/ mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis. | BACKGROUND: Recently, mutations in the /"filaggrin"/ gene (/"FLG"/) have been shown to be a major predisposing factor for atopic dermatitis (AD). OBJECTIVE: In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals. RESULTS: We found a strong association of the /"FLG"/ mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant /"asthma"/ compared with those without this co-morbidity. CONCLUSION: Our data confirm and extend the knowledge of the influence of /"FLG"/ mutations in AD. | [
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"text_name": "asthma"
} | No |
19875396 | Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. | A patient with an SCN5A p.W822X nonsense mutation, localized in the transmembrane region DII-S4 of the Na(v)1.5 sodium channel and leading to a non-expression of the mutant allele, was prescribed the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Floxyfral), 100 mg per day. His normal baseline ECG changed to a characteristic Brugada-Type-1-ECG pattern. To investigate whether fluvoxamine may reduce the cardiac sodium current, the effect of this drug was studied on the wild-type voltage-gated cardiac sodium channel Na(v)1.5 stably expressed in HEK293 cells. Patch-clamp recording showed a 50% inhibition of the current at a concentration of 57.3 microM. In our patient, no arrhythmia occurred but the proarrhythmic potential of SSRI in patients with SCN5A mutations cannot be excluded. Therefore, we advise 12-lead ECG control after administering SSRI in these patients. | /"Brugada syndrome"/ ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. | A patient with an /"SCN5A"/ p.W822X nonsense mutation, localized in the transmembrane region DII-S4 of the Na(v)1.5 sodium channel and leading to a non-expression of the mutant allele, was prescribed the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Floxyfral), 100 mg per day. His normal baseline ECG changed to a characteristic Brugada-Type-1-ECG pattern. To investigate whether fluvoxamine may reduce the cardiac sodium current, the effect of this drug was studied on the wild-type voltage-gated cardiac sodium channel Na(v)1.5 stably expressed in HEK293 cells. Patch-clamp recording showed a 50% inhibition of the current at a concentration of 57.3 microM. In our patient, no arrhythmia occurred but the proarrhythmic potential of SSRI in patients with /"SCN5A"/ mutations cannot be excluded. Therefore, we advise 12-lead ECG control after administering SSRI in these patients. | [
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19875396 | Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. | A patient with an SCN5A p.W822X nonsense mutation, localized in the transmembrane region DII-S4 of the Na(v)1.5 sodium channel and leading to a non-expression of the mutant allele, was prescribed the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Floxyfral), 100 mg per day. His normal baseline ECG changed to a characteristic Brugada-Type-1-ECG pattern. To investigate whether fluvoxamine may reduce the cardiac sodium current, the effect of this drug was studied on the wild-type voltage-gated cardiac sodium channel Na(v)1.5 stably expressed in HEK293 cells. Patch-clamp recording showed a 50% inhibition of the current at a concentration of 57.3 microM. In our patient, no arrhythmia occurred but the proarrhythmic potential of SSRI in patients with SCN5A mutations cannot be excluded. Therefore, we advise 12-lead ECG control after administering SSRI in these patients. | /"Brugada syndrome"/ ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine. | A patient with an SCN5A p.W822X nonsense mutation, localized in the transmembrane region DII-S4 of the /"Na(v)1.5"/ sodium channel and leading to a non-expression of the mutant allele, was prescribed the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Floxyfral), 100 mg per day. His normal baseline ECG changed to a characteristic Brugada-Type-1-ECG pattern. To investigate whether fluvoxamine may reduce the cardiac sodium current, the effect of this drug was studied on the wild-type voltage-gated cardiac sodium channel /"Na(v)1.5"/ stably expressed in HEK293 cells. Patch-clamp recording showed a 50% inhibition of the current at a concentration of 57.3 microM. In our patient, no arrhythmia occurred but the proarrhythmic potential of SSRI in patients with SCN5A mutations cannot be excluded. Therefore, we advise 12-lead ECG control after administering SSRI in these patients. | [
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19891592 | Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence. | Association among polymorphisms at /"MYH9"/, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (/"MYH9"/) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without /"cleft palate"/ in several populations. Our study aimed to confirm the contribution of /"MYH9"/ and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of /"MYH9"/ and influence of environmental factors in nonsyndromic orofacial cleft incidence. | [
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} | Yes |
19891592 | Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence. | Association among polymorphisms at /"MYH9"/, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (/"MYH9"/) and environmental factors have been shown to be associated with /"nonsyndromic cleft lip"/ with or without cleft palate in several populations. Our study aimed to confirm the contribution of /"MYH9"/ and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of /"MYH9"/ and influence of environmental factors in nonsyndromic orofacial cleft incidence. | [
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} | Yes |
19891592 | Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence. | Association among polymorphisms at /"MYH9"/, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (/"MYH9"/) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of /"MYH9"/ and environmental factors to nonsyndromic /"orofacial cleft"/ risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of /"MYH9"/ and influence of environmental factors in nonsyndromic /"orofacial cleft"/ incidence. | [
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} | No |
19891592 | Association among polymorphisms at MYH9, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence. | Association among polymorphisms at /"MYH9"/, environmental factors, and nonsyndromic orofacial clefts in western China. | Myosin heavy chain 9, nonmuscle (/"MYH9"/) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of /"MYH9"/ and environmental factors to nonsyndromic /"orofacial cleft"/ risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of /"MYH9"/ and influence of environmental factors in nonsyndromic /"orofacial cleft"/ incidence. | [
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19892319 | Catechol-o-methyltransferase valine(158)methionine genotype and resting regional cerebral blood flow in medication-free patients with schizophrenia. | BACKGROUND: A valine(158)methionine (val(158)met) polymorphism in catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with schizophrenia. Consistent with schizophrenia itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in schizophrenia have not yet been characterized. METHODS: Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the COMT val(158)met polymorphism and underwent two 60-second radiolabeled water ([(15)O]H(2)O) regional cerebral blood flow (rCBF) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate. RESULTS: In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus. CONCLUSIONS: In schizophrenia, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity. | /"Catechol-o-methyltransferase"/ valine(158)methionine genotype and resting regional cerebral blood flow in medication-free patients with /"schizophrenia"/. | BACKGROUND: A valine(158)methionine (val(158)met) polymorphism in /"catechol-O-methyltransferase"/ (/"COMT"/) modulates cortical dopaminergic catabolism and has been associated with /"schizophrenia"/. Consistent with /"schizophrenia"/ itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in /"schizophrenia"/ have not yet been characterized. METHODS: Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the /"COMT"/ val(158)met polymorphism and underwent two 60-second radiolabeled water ([(15)O]H(2)O) regional cerebral blood flow (rCBF) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using /"COMT"/ genotype as a covariate. RESULTS: In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus. CONCLUSIONS: In /"schizophrenia"/, brain structures important for executive and affective processing show activity that is differentially predicted by /"COMT"/ allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity. | [
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19892319 | Catechol-o-methyltransferase valine(158)methionine genotype and resting regional cerebral blood flow in medication-free patients with schizophrenia. | BACKGROUND: A valine(158)methionine (val(158)met) polymorphism in catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with schizophrenia. Consistent with schizophrenia itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in schizophrenia have not yet been characterized. METHODS: Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the COMT val(158)met polymorphism and underwent two 60-second radiolabeled water ([(15)O]H(2)O) regional cerebral blood flow (rCBF) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate. RESULTS: In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater rCBF in the amygdala and parahippocampal gyrus. CONCLUSIONS: In schizophrenia, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity. | Catechol-o-methyltransferase valine(158)methionine genotype and resting regional cerebral blood flow in medication-free patients with /"schizophrenia"/. | BACKGROUND: A valine(158)methionine (val(158)met) polymorphism in catechol-O-methyltransferase (COMT) modulates cortical dopaminergic catabolism and has been associated with /"schizophrenia"/. Consistent with /"schizophrenia"/ itself, during cognitive tasks, the risk (val) allele predicts less efficient prefrontal cortex (PFC) physiology and worse performance, while during aversive stimuli viewing, this allele predicts less limbic activation. Task-independent effects of this polymorphism in /"schizophrenia"/ have not yet been characterized. METHODS: Twenty-five medication-free patients (28 +/- 6 years; 19 male patients) and 47 healthy individuals (29 +/- 8 years; 33 male individuals) were genotyped for the COMT val(158)met polymorphism and underwent two 60-second radiolabeled water ([(15)O]H(2)O) regional cerebral blood flow (/"rCBF"/) positron emission tomography scans (10 mCi/scan) during rest. Data were analyzed with a random-effects general linear model using COMT genotype as a covariate. RESULTS: In patients, but not healthy individuals, val (risk) allele load predicted less regional cerebral blood flow in the right dorsolateral PFC, right superior temporal gyrus, and left precuneus, but greater /"rCBF"/ in the amygdala and parahippocampal gyrus. CONCLUSIONS: In /"schizophrenia"/, brain structures important for executive and affective processing show activity that is differentially predicted by COMT allelic variation in an opposing manner even at rest, providing evidence for the salience of prefrontal dopaminergic tone in task-independent, basal-level neural activity. | [
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19892845 | Alternative splicing and molecular characterization of splice site variants: BRCA1 c.591C>T as a case study. | BACKGROUND: Deleterious mutations in BRCA1 (breast cancer 1, early onset; MIM 113705) increase breast and ovarian cancer [B(O)C] risk; however, many variants cannot be readily classified as deleterious or neutral. Unclassified variants (UVs) pose serious problems in genetic counseling. RNA-splicing analysis is essential for the assessment of many UVs. METHODS: Denaturing gradient gel electrophoresis was used to genotype the BRCA1 c.591C>T variant in 685 index cases of B(O)C families, 326 sporadic breast cancer cases, and 450 healthy controls from Spain. In silico tools were used to predict the effect of the c.591C>T variant on splicing. In vitro splicing analysis was performed in 7 c.591C>T carriers and 10 noncarriers. cDNAs were PCR-amplified with primers designed to detect BRCA1 alternative splicing isoforms. The products were analyzed by capillary electrophoresis. Peak areas were used to quantify the relative abundance of each isoform. Sequencing through exonic single-nucleotide polymorphisms (SNPs) enabled us to discriminate wild-type and variant transcripts. RESULTS: c.591C>T was detected in B(O)C families (1.5%), breast cancer cases (0.3%), and controls (0.9%). c.591C>T induced BRCA1 exon 9 skipping and modified the relative expression of Delta(9,10), Delta(9,10,11B), Delta11B, and full-length isoforms. The mean ratio of Delta(9,10) to the full-length isoform increased from 0.25 in noncarriers to 1.5 in carriers. The mean Delta(9,10,11B)/Delta11B ratio increased from 0.2 to 4. Overall expression levels of c.591C>T and wild-type alleles were similar. CONCLUSIONS: Our data support a nonpathogenic role for the BRCA1 c.591C>T variant. Naturally occurring alternative splicing isoforms need to be considered when assessing the role of BRCA1 UVs on splicing. | Alternative splicing and molecular characterization of splice site variants: /"BRCA1"/A1"/ c.591C>T as a case study. | BACKGROUND: Deleterious mutations in /"BRCA1"/A1"/ (/"breast cancer 1"/ 1"/, early onset; MIM 113705) increase breast and ovarian cancer [B(O)C] risk; however, many variants cannot be readily classified as deleterious or neutral. Unclassified variants (UVs) pose serious problems in genetic counseling. RNA-splicing analysis is essential for the assessment of many UVs. METHODS: Denaturing gradient gel electrophoresis was used to genotype the /"BRCA1"/A1"/ c.591C>T variant in 685 index cases of B(O)C families, 326 /"sporadic breast cancer"/ cases, and 450 healthy controls from Spain. In silico tools were used to predict the effect of the c.591C>T variant on splicing. In vitro splicing analysis was performed in 7 c.591C>T carriers and 10 noncarriers. cDNAs were PCR-amplified with primers designed to detect /"BRCA1"/A1"/ alternative splicing isoforms. The products were analyzed by capillary electrophoresis. Peak areas were used to quantify the relative abundance of each isoform. Sequencing through exonic single-nucleotide polymorphisms (SNPs) enabled us to discriminate wild-type and variant transcripts. RESULTS: c.591C>T was detected in B(O)C families (1.5%), /"breast cancer"/ cases (0.3%), and controls (0.9%). c.591C>T induced /"BRCA1"/A1"/ exon 9 skipping and modified the relative expression of Delta(9,10), Delta(9,10,11B), Delta11B, and full-length isoforms. The mean ratio of Delta(9,10) to the full-length isoform increased from 0.25 in noncarriers to 1.5 in carriers. The mean Delta(9,10,11B)/Delta11B ratio increased from 0.2 to 4. Overall expression levels of c.591C>T and wild-type alleles were similar. CONCLUSIONS: Our data support a nonpathogenic role for the /"BRCA1"/A1"/ c.591C>T variant. Naturally occurring alternative splicing isoforms need to be considered when assessing the role of /"BRCA1"/A1"/ UVs on splicing. | [
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