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12767526 | Association of the genetic polymorphism in cytochrome P450 (CYP) 1A1 with risk of familial prostate cancer in a Japanese population: a case-control study. | Association between genetic polymorphisms of CYP1A1 and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of CYP1A1 showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic cancer had a significant association with mutated alleles of m1 and m2. These finding suggested that CYP1A1 polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer. | Association of the genetic polymorphism in /"cytochrome P450 (CYP) 1A1"/ with risk of familial prostate cancer in a Japanese population: a case-control study. | Association between genetic polymorphisms of /"CYP1A1"/ and familial prostate cancer risk was examined by a case-control study of 185 individuals. Although the individual analysis of m1 or m2 genotype of /"CYP1A1"/ showed no significant association with prostate cancer risk, the presence of any mutated alleles significantly increased prostate cancer risk in comparison with wild-type genotypes by combination analysis (odds ratio [OR]=2.38; 95% confidence interval [CI]=1.72-3.29; P=0.0069). Furthermore, metastatic /"cancer"/ had a significant association with mutated alleles of m1 and m2. These finding suggested that /"CYP1A1"/ polymorphisms has an association with prostate cancer risk, especially with progression of prostate cancer. | [
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12771801 | Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population. | PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer. | Association of V89L /"SRD5A2"/ polymorphism with /"prostate cancer"/ development in a Japanese population. | PURPOSE: The /"SRD5A2"/ gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of /"prostate cancer"/ or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with /"prostate cancer"/, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with /"prostate cancer"/ and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for /"prostate cancer"/ compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of /"prostate cancer"/, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the /"SRD5A2"/ gene may dominantly increase the risk of /"prostate cancer"/. | [
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12771801 | Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population. | PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer. | Association of V89L /"SRD5A2"/ polymorphism with prostate cancer development in a Japanese population. | PURPOSE: The /"SRD5A2"/ gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or /"benign prostatic hyperplasia"/ (/"BPH"/) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with /"BPH"/ and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with /"BPH"/ and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of /"BPH"/ in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the /"SRD5A2"/ gene may dominantly increase the risk of prostate cancer. | [
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12782962 | Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia. | OBJECTIVES: Glutamatergic dysfunction is one of the major hypotheses of schizophrenia pathophysiology. We have been conducting systematic studies on the association between glutamate receptors and schizophrenia. We focused on the metabotropic glutamate receptor type 3 gene (GRM3) as a candidate for schizophrenia susceptibility. METHODS: We genotyped Japanese schizophrenics (n=100) and controls (n=100) for six single nucleotide polymorphisms (SNPs) located in the GRM3 region at intervals of approximately 50 kb. Statistical differences in genotype, allele and haplotype frequencies between cases and controls were evaluated by the chi2 test and Fisher's exact probability test at a significance level of 0.05. Haplotype frequencies were estimated by the EM algorithm. RESULTS: A case-control association study identified a significant difference in allele frequency distribution of a SNP, rs1468412, between schizophrenics and controls (P=0.011). We also observed significant differences in haplotype frequencies estimated from SNP frequencies between schizophrenics and controls. The haplotype constructed from three SNPs, including rs1468412, showed a significant association with schizophrenia (P=8.30 x 10-4). CONCLUSIONS: Our data indicate that at least one susceptibility locus for schizophrenia is situated within or very close to the GRM3 region in the Japanese patients. | Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (/"GRM3"/) with /"schizophrenia"/. | OBJECTIVES: Glutamatergic dysfunction is one of the major hypotheses of /"schizophrenia"/ pathophysiology. We have been conducting systematic studies on the association between glutamate receptors and /"schizophrenia"/. We focused on the metabotropic glutamate receptor type 3 gene (/"GRM3"/) as a candidate for /"schizophrenia"/ susceptibility. METHODS: We genotyped Japanese /"schizophrenics"/ (n=100) and controls (n=100) for six single nucleotide polymorphisms (SNPs) located in the /"GRM3"/ region at intervals of approximately 50 kb. Statistical differences in genotype, allele and haplotype frequencies between cases and controls were evaluated by the chi2 test and Fisher's exact probability test at a significance level of 0.05. Haplotype frequencies were estimated by the EM algorithm. RESULTS: A case-control association study identified a significant difference in allele frequency distribution of a SNP, rs1468412, between /"schizophrenics"/ and controls (P=0.011). We also observed significant differences in haplotype frequencies estimated from SNP frequencies between /"schizophrenics"/ and controls. The haplotype constructed from three SNPs, including rs1468412, showed a significant association with /"schizophrenia"/ (P=8.30 x 10-4). CONCLUSIONS: Our data indicate that at least one susceptibility locus for /"schizophrenia"/ is situated within or very close to the /"GRM3"/ region in the Japanese patients. | [
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12782962 | Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (GRM3) with schizophrenia. | OBJECTIVES: Glutamatergic dysfunction is one of the major hypotheses of schizophrenia pathophysiology. We have been conducting systematic studies on the association between glutamate receptors and schizophrenia. We focused on the metabotropic glutamate receptor type 3 gene (GRM3) as a candidate for schizophrenia susceptibility. METHODS: We genotyped Japanese schizophrenics (n=100) and controls (n=100) for six single nucleotide polymorphisms (SNPs) located in the GRM3 region at intervals of approximately 50 kb. Statistical differences in genotype, allele and haplotype frequencies between cases and controls were evaluated by the chi2 test and Fisher's exact probability test at a significance level of 0.05. Haplotype frequencies were estimated by the EM algorithm. RESULTS: A case-control association study identified a significant difference in allele frequency distribution of a SNP, rs1468412, between schizophrenics and controls (P=0.011). We also observed significant differences in haplotype frequencies estimated from SNP frequencies between schizophrenics and controls. The haplotype constructed from three SNPs, including rs1468412, showed a significant association with schizophrenia (P=8.30 x 10-4). CONCLUSIONS: Our data indicate that at least one susceptibility locus for schizophrenia is situated within or very close to the GRM3 region in the Japanese patients. | Positive associations of polymorphisms in the metabotropic glutamate receptor type 3 gene (/"GRM3"/) with schizophrenia. | OBJECTIVES: /"Glutamatergic dysfunction"/ is one of the major hypotheses of schizophrenia pathophysiology. We have been conducting systematic studies on the association between glutamate receptors and schizophrenia. We focused on the metabotropic glutamate receptor type 3 gene (/"GRM3"/) as a candidate for schizophrenia susceptibility. METHODS: We genotyped Japanese schizophrenics (n=100) and controls (n=100) for six single nucleotide polymorphisms (SNPs) located in the /"GRM3"/ region at intervals of approximately 50 kb. Statistical differences in genotype, allele and haplotype frequencies between cases and controls were evaluated by the chi2 test and Fisher's exact probability test at a significance level of 0.05. Haplotype frequencies were estimated by the EM algorithm. RESULTS: A case-control association study identified a significant difference in allele frequency distribution of a SNP, rs1468412, between schizophrenics and controls (P=0.011). We also observed significant differences in haplotype frequencies estimated from SNP frequencies between schizophrenics and controls. The haplotype constructed from three SNPs, including rs1468412, showed a significant association with schizophrenia (P=8.30 x 10-4). CONCLUSIONS: Our data indicate that at least one susceptibility locus for schizophrenia is situated within or very close to the /"GRM3"/ region in the Japanese patients. | [
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12789280 | Genetics of melanoma predisposition. | Predisposition to melanoma is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on identification of genes that confer a more modest contribution to melanoma risk, such as those encoding proteins involved in pigmentation, DNA repair, cell growth and differentiation or detoxification of metabolites. One such pigmentation gene, MC1R, has not only been found to be a low penetrance melanoma gene but has also been shown to act as a genetic modifier of melanoma risk in individuals carrying CDKN2A mutations. Most recently, an environmental agent, ultraviolet radiation, has also been established as a modifier of melanoma risk in CDKN2A mutation carriers. Hence, melanoma is turning out to be an excellent paradigm for studying gene-gene and gene-environment interactions. | Genetics of /"melanoma"/ predisposition. | Predisposition to /"melanoma"/ is genetically heterogeneous. Two high penetrance susceptibility genes, /"CDKN2A"/ and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on identification of genes that confer a more modest contribution to /"melanoma"/ risk, such as those encoding proteins involved in pigmentation, DNA repair, cell growth and differentiation or detoxification of metabolites. One such pigmentation gene, MC1R, has not only been found to be a low penetrance /"melanoma"/ gene but has also been shown to act as a genetic modifier of /"melanoma"/ risk in individuals carrying /"CDKN2A"/ mutations. Most recently, an environmental agent, ultraviolet radiation, has also been established as a modifier of /"melanoma"/ risk in /"CDKN2A"/ mutation carriers. Hence, /"melanoma"/ is turning out to be an excellent paradigm for studying gene-gene and gene-environment interactions. | [
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12789280 | Genetics of melanoma predisposition. | Predisposition to melanoma is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on identification of genes that confer a more modest contribution to melanoma risk, such as those encoding proteins involved in pigmentation, DNA repair, cell growth and differentiation or detoxification of metabolites. One such pigmentation gene, MC1R, has not only been found to be a low penetrance melanoma gene but has also been shown to act as a genetic modifier of melanoma risk in individuals carrying CDKN2A mutations. Most recently, an environmental agent, ultraviolet radiation, has also been established as a modifier of melanoma risk in CDKN2A mutation carriers. Hence, melanoma is turning out to be an excellent paradigm for studying gene-gene and gene-environment interactions. | Genetics of /"melanoma"/ predisposition. | Predisposition to /"melanoma"/ is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and /"CDK4"/, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on identification of genes that confer a more modest contribution to /"melanoma"/ risk, such as those encoding proteins involved in pigmentation, DNA repair, cell growth and differentiation or detoxification of metabolites. One such pigmentation gene, MC1R, has not only been found to be a low penetrance /"melanoma"/ gene but has also been shown to act as a genetic modifier of /"melanoma"/ risk in individuals carrying CDKN2A mutations. Most recently, an environmental agent, ultraviolet radiation, has also been established as a modifier of /"melanoma"/ risk in CDKN2A mutation carriers. Hence, /"melanoma"/ is turning out to be an excellent paradigm for studying gene-gene and gene-environment interactions. | [
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12793904 | C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer. | BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression. METHODS: We investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease. RESULTS: An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). CONCLUSION: The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin. | C766T /"low-density lipoprotein receptor-related protein 1"/ (/"LRP1"/) gene polymorphism and susceptibility to /"breast cancer"/. | BACKGROUND: /"Low-density lipoprotein receptor-related protein 1"/ (/"LRP1"/) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of /"LRP1"/ is related to invasiveness of cancer cells. However, recent data on /"LRP1"/ suggest that this receptor can also be involved in tumor establishment and progression. METHODS: We investigated an association between the C766T polymorphism of the third exon of the /"LRP1"/ gene and /"breast cancer"/ in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with /"breast cancer"/ and in 183 age-compatible women without a history of any cancer disease. RESULTS: An increase in /"LRP1"/ T allele frequency in subjects with /"breast cancer"/ was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). CONCLUSION: The T allele of the C766T polymorphism in the /"LRP1"/ gene is associated with an increased risk of /"breast cancer"/ development in women of Caucasian origin. | [
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12793904 | C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer. | BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression. METHODS: We investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease. RESULTS: An increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). CONCLUSION: The T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin. | C766T /"low-density lipoprotein receptor-related protein 1"/ (/"LRP1"/) gene polymorphism and susceptibility to breast cancer. | BACKGROUND: /"Low-density lipoprotein receptor-related protein 1"/ (/"LRP1"/) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of /"LRP1"/ is related to invasiveness of /"cancer"/ cells. However, recent data on /"LRP1"/ suggest that this receptor can also be involved in /"tumor"/ establishment and progression. METHODS: We investigated an association between the C766T polymorphism of the third exon of the /"LRP1"/ gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any /"cancer disease"/. RESULTS: An increase in /"LRP1"/ T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112-2.732). CONCLUSION: The T allele of the C766T polymorphism in the /"LRP1"/ gene is associated with an increased risk of breast cancer development in women of Caucasian origin. | [
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12800193 | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | Expression profiling of CC531 /"colon carcinoma"/ cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during /"colon carcinogenesis"/, the wnt and the /"ki-ras"/ signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a /"ki-ras"/ (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | [
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12800193 | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | Expression profiling of CC531 /"colon carcinoma"/ cells reveals similar regulation of /"beta-catenin"/ target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during /"colon carcinogenesis"/, the wnt and the ki-ras signaling pathways. We found both a prototypic /"beta-catenin"/ (/"Ctnnb1"/) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the /"beta-catenin"/ and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | [
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12800193 | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of /"beta-catenin"/ target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of /"tumor"/ growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic /"beta-catenin"/ (/"Ctnnb1"/) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the /"beta-catenin"/ and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | [
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12800193 | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. | The CC531 cell line has been widely used to study different aspects of /"tumor"/ growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, /"c-myc"/, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. The microarray data are available (http://ncbi.nlm.nih.gov/geo/). | [
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12802709 | Relationship between tumor necrosis factor-alpha genotype and success of emergent cerclage. | The guanine to adenine substitution at the -308 position in the tumor necrosis factor-alpha (TNF-alpha) gene promoter region results in a 5-fold greater cytokine response to an inciting event. We investigated whether this polymorphism is associated with cervical incompetence and adverse pregnancy outcome after emergent cerclage. Women with a diagnosis of cervical incompetence requiring an emergent cerclage between 15 and 24 weeks were enrolled. Women without pregnancy complications were recruited as controls. DNA extraction from peripheral blood and polymerase chain reaction (PCR) amplification of a 144-base pair segment of the TNF-alpha gene were performed with subsequent sequencing. Twenty-three women underwent emergent cerclage and participated in the study, 13 (57%) of whom delivered after 28 weeks. Twenty-three women served as controls. There were no differences in the TNF-alpha polymorphism between women with cervical incompetence and controls or between women with cervical incompetence who delivered before versus after 28 weeks. The TNF-alpha polymorphism was not associated with cervical incompetence or with delivery prior to 28 weeks in women who received an emergent cerclage. | Relationship between /"tumor necrosis factor-alpha"/ genotype and success of emergent cerclage. | The guanine to adenine substitution at the -308 position in the /"tumor necrosis factor-alpha"/ (/"TNF-alpha"/) gene promoter region results in a 5-fold greater cytokine response to an inciting event. We investigated whether this polymorphism is associated with /"cervical incompetence"/ and adverse pregnancy outcome after emergent cerclage. Women with a diagnosis of /"cervical incompetence"/ requiring an emergent cerclage between 15 and 24 weeks were enrolled. Women without pregnancy complications were recruited as controls. DNA extraction from peripheral blood and polymerase chain reaction (PCR) amplification of a 144-base pair segment of the /"TNF-alpha"/ gene were performed with subsequent sequencing. Twenty-three women underwent emergent cerclage and participated in the study, 13 (57%) of whom delivered after 28 weeks. Twenty-three women served as controls. There were no differences in the /"TNF-alpha"/ polymorphism between women with /"cervical incompetence"/ and controls or between women with /"cervical incompetence"/ who delivered before versus after 28 weeks. The /"TNF-alpha"/ polymorphism was not associated with /"cervical incompetence"/ or with delivery prior to 28 weeks in women who received an emergent cerclage. | [
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12815595 | The molecular basis of glutamate formiminotransferase deficiency. | Glutamate formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative glutamate formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in glutamate formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. | The molecular basis of /"glutamate formiminotransferase deficiency"/. | /"Glutamate formiminotransferase deficiency"/, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (/"FTCD"/). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human /"FTCD"/ gene in three patients with putative /"glutamate formiminotransferase deficiency"/. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine /"FTCD"/ and expression in E. coli showed that the R135C mutation reduced formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in /"glutamate formiminotransferase deficiency"/ and demonstrate that mutations in /"FTCD"/ represent the molecular basis for the mild phenotype of this disease. | [
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12815595 | The molecular basis of glutamate formiminotransferase deficiency. | Glutamate formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (FTCD). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human FTCD gene in three patients with putative glutamate formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine FTCD and expression in E. coli showed that the R135C mutation reduced formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in glutamate formiminotransferase deficiency and demonstrate that mutations in FTCD represent the molecular basis for the mild phenotype of this disease. | The molecular basis of glutamate formiminotransferase deficiency. | Glutamate formiminotransferase deficiency, an autosomal recessive disorder and the second most common inborn error of folate metabolism, is presumed to be due to defects in the bifunctional enzyme glutamate formiminotransferase-cyclodeaminase (/"FTCD"/). Features of a severe phenotype, first identified in patients of Japanese descent, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and /"mental retardation"/. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. We found mutations in the human /"FTCD"/ gene in three patients with putative glutamate formiminotransferase deficiency. Two siblings were heterozygous for missense mutations, c.457C>T (R135C) and c.940G>C (R299P). Mutagenesis of porcine /"FTCD"/ and expression in E. coli showed that the R135C mutation reduced formiminotransferase activity to 61% of wild-type, whereas the R299P mutation reduced this activity to 57% of wild-type. The third patient was hemizygous for c.1033insG, with quantitative PCR indicating that the other allele contained a deletion. These mutations are the first identified in glutamate formiminotransferase deficiency and demonstrate that mutations in /"FTCD"/ represent the molecular basis for the mild phenotype of this disease. | [
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12824768 | Polymorphism in the BACE gene influences the risk for Alzheimer's disease. | Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase. Variations of the BACE gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different BACE polymorphisms with AD. BACE exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by BACE genotype. It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels. | Polymorphism in the /"BACE"/ gene influences the risk for /"Alzheimer's disease"/. | Pathological characteristics of /"Alzheimer's disease"/ (/"AD"/) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. /"BACE"/ (/"beta-site APP cleaving enzyme"/) was identified as the beta-secretase. Variations of the /"BACE"/ gene might influence activity and function of the protein and, thus, might influence the pathogenesis of /"AD"/. Consequently, we investigated the association of different /"BACE"/ polymorphisms with /"AD"/. /"BACE"/ exon 5 polymorphism influenced the risk of /"AD"/. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by /"BACE"/ genotype. It appears that /"BACE"/ polymorphism plays a more important role in the development of /"AD"/ than previously assumed, possibly by influencing Abeta(42) levels. | [
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} | Yes |
12824768 | Polymorphism in the BACE gene influences the risk for Alzheimer's disease. | Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and amyloid-beta (Abeta) plaques. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. BACE (beta-site APP cleaving enzyme) was identified as the beta-secretase. Variations of the BACE gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different BACE polymorphisms with AD. BACE exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by BACE genotype. It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels. | Polymorphism in the /"BACE"/ gene influences the risk for Alzheimer's disease. | Pathological characteristics of Alzheimer's disease (AD) are neurofibrillary tangles and /"amyloid-beta (Abeta) plaques"/. Abeta is generated by cleavage of the amyloid precursor protein by beta- and gamma-secretases. /"BACE"/ (/"beta-site APP cleaving enzyme"/) was identified as the beta-secretase. Variations of the /"BACE"/ gene might influence activity and function of the protein and, thus, might influence the pathogenesis of AD. Consequently, we investigated the association of different /"BACE"/ polymorphisms with AD. /"BACE"/ exon 5 polymorphism influenced the risk of AD. This effect was most pronounced in apolipoprotein E4 allele carriers. Furthermore, Abeta(42) CSF levels were influenced by /"BACE"/ genotype. It appears that /"BACE"/ polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of /"MTHFR"/, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/ C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with /"acute lymphoblastic leukemia"/ (/"ALL"/) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of /"MTHFR"/ genotype was insignificantly higher in /"ALL"/ (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between /"ALL"/ patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in /"ALL"/ patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of /"ALL"/ (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in /"ALL"/ patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of /"childhood ALL"/ and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, /"GSTT1"/, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and /"GSTT1"/ null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with /"acute lymphoblastic leukemia"/ (/"ALL"/) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in /"ALL"/ (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between /"ALL"/ patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although /"GSTT1"/ null genotype was insignificantly lower in /"ALL"/ patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of /"ALL"/ (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in /"ALL"/ patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of /"childhood ALL"/ and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except /"GSTT1"/ null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, /"GSTM1"/, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (/"GSTM1"/ and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with /"acute lymphoblastic leukemia"/ (/"ALL"/) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in /"ALL"/ (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the /"GSTM1"/ null genotype was detected between /"ALL"/ patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in /"ALL"/ patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of /"ALL"/ (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in /"ALL"/ patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of /"childhood ALL"/ and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, GSTT1, /"GSTP1"/, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, /"GSTP1"/ Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with /"acute lymphoblastic leukemia"/ (/"ALL"/) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in /"ALL"/ (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between /"ALL"/ patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in /"ALL"/ patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of /"GSTP1"/ genotype did not differ significantly between groups of /"ALL"/ (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in /"ALL"/ patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of /"childhood ALL"/ and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and /"CYP1A1"/ genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (/"CYP1A1"/*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with /"acute lymphoblastic leukemia"/ (/"ALL"/) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in /"ALL"/ (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between /"ALL"/ patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in /"ALL"/ patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of /"ALL"/ (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous /"CYP1A1"/*2A genotype was underrepresented in /"ALL"/ patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of /"childhood ALL"/ and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for /"CYP1A1"/ genotypes that may play protective roles in the development of ANLL in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, GSTT1, /"GSTP1"/, and CYP1A1 genotypes in childhood /"acute leukemia"/. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, /"GSTP1"/ Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with /"acute nonlymphoblastic leukemia"/ (/"ANLL"/) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and /"ANLL"/ (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in /"ANLL"/ patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in /"ANLL"/ patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of /"GSTP1"/ genotype did not differ significantly between groups of ALL (3.7%), /"ANLL"/ patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in /"ANLL"/ patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and /"ANLL"/. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of /"acute leukemia"/ except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of /"ANLL"/ in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, /"GSTM1"/, GSTT1, GSTP1, and CYP1A1 genotypes in childhood /"acute leukemia"/. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (/"GSTM1"/ and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with /"acute nonlymphoblastic leukemia"/ (/"ANLL"/) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and /"ANLL"/ (6.3%) than in controls (4.4%). Equal distribution of the /"GSTM1"/ null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in /"ANLL"/ patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in /"ANLL"/ patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), /"ANLL"/ patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in /"ANLL"/ patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and /"ANLL"/. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of /"acute leukemia"/ except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of /"ANLL"/ in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, /"GSTT1"/, GSTP1, and CYP1A1 genotypes in childhood /"acute leukemia"/. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and /"GSTT1"/ null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with /"acute nonlymphoblastic leukemia"/ (/"ANLL"/) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and /"ANLL"/ (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in /"ANLL"/ patients (61.3%). Although /"GSTT1"/ null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in /"ANLL"/ patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), /"ANLL"/ patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in /"ANLL"/ patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and /"ANLL"/. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of /"acute leukemia"/ except /"GSTT1"/ null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of /"ANLL"/ in Turkish children. | [
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12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, /"GSTT1"/, GSTP1, and CYP1A1 genotypes in childhood /"acute leukemia"/. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and /"GSTT1"/ null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with /"acute nonlymphoblastic leukemia"/ (/"ANLL"/) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and /"ANLL"/ (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in /"ANLL"/ patients (61.3%). Although /"GSTT1"/ null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in /"ANLL"/ patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), /"ANLL"/ patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in /"ANLL"/ patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and /"ANLL"/. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of /"acute leukemia"/ except /"GSTT1"/ null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of /"ANLL"/ in Turkish children. | [
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} | No |
12827651 | Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children. | Characterization of MTHFR, GSTM1, GSTT1, /"GSTP1"/, and CYP1A1 genotypes in childhood /"acute leukemia"/. | The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, /"GSTP1"/ Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with /"acute nonlymphoblastic leukemia"/ (/"ANLL"/) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and /"ANLL"/ (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in /"ANLL"/ patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in /"ANLL"/ patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of /"GSTP1"/ genotype did not differ significantly between groups of ALL (3.7%), /"ANLL"/ patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in /"ANLL"/ patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and /"ANLL"/. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of /"acute leukemia"/ except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of /"ANLL"/ in Turkish children. | [
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12828656 | Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | Polymorphisms in the +252(A/G) /"lymphotoxin-alpha"/ and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to /"chronic periodontitis"/ in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between /"chronic periodontitis"/ and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the /"lymphotoxin alpha"/ (/"LT-alpha"/) gene. Genomic DNA was obtained from 132 patients with /"chronic periodontitis"/ together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with /"chronic periodontitis"/, whereas the frequency distribution of the /"LT-alpha"/ (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the /"LT-alpha"/ 1/1 genotype was significantly lower in the group of patients with /"chronic periodontitis"/ (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and /"LT-alpha"/) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and /"LT-alpha"/ gene polymorphisms may influence the susceptibility to /"chronic periodontitis"/. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the /"LT-alpha"/ gene is a more informative marker and it may be one of the protective genetic factors against /"chronic periodontitis"/ in our population. | [
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12828656 | Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) /"tumor necrosis factor"/-alpha genes and susceptibility to /"chronic periodontitis"/ in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. /"Tumor necrosis factor"/ (/"TNF"/), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between /"chronic periodontitis"/ and two previously described bi-allelic polymorphisms in the /"TNF"/ locus: a G to A transition at position -308 in the 5'promoter region of the /"TNF-alpha"/ gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with /"chronic periodontitis"/ together with 114 age- and gender-matched unrelated control subjects. RESULTS: The /"TNF-alpha"/ (-308G/A) polymorphism itself showed no association with /"chronic periodontitis"/, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with /"chronic periodontitis"/ (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (/"TNF-alpha"/ and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the /"TNF-alpha"/ and LT-alpha gene polymorphisms may influence the susceptibility to /"chronic periodontitis"/. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against /"chronic periodontitis"/ in our population. | [
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12828656 | Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | Polymorphisms in the +252(A/G) /"lymphotoxin-alpha"/ and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible /"attachment loss"/, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the /"lymphotoxin alpha"/ (/"LT-alpha"/) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the /"LT-alpha"/ (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the /"LT-alpha"/ 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and /"LT-alpha"/) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and /"LT-alpha"/ gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the /"LT-alpha"/ gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | [
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12828656 | Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | Polymorphisms in the +252(A/G) /"lymphotoxin-alpha"/ and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. | BACKGROUND: Periodontitis is an inflammatory disease that leads to irreversible attachment loss, /"bone destruction"/ and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease. METHODS: In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the /"lymphotoxin alpha"/ (/"LT-alpha"/) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects. RESULTS: The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the /"LT-alpha"/ (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the /"LT-alpha"/ 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and /"LT-alpha"/) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01). CONCLUSION: Our data suggest that combined genotypes composed of the TNF-alpha and /"LT-alpha"/ gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the /"LT-alpha"/ gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population. | [
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12843182 | A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro. | Camurati-Engelmann disease (CED) is a rare autosomal dominant disorder characterized by bone pain and osteosclerosis affecting the diaphysis of long bones. CED is caused by various missense mutations in the TGFB1 gene that encodes TGFbeta1, the most common of which is an arginine-cysteine amino acid change at codon 218 (R218C) in the latency-associated peptide domain of TGFbeta1. We studied osteoclast formation in vitro from peripheral blood mononuclear cells obtained from three related CED patients harboring the R218C mutation, in comparison with one family-based and several unrelated controls. Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in CED patients, and the increase in osteoclast formation was inhibited by soluble TGFbeta type II receptor. Total serum TGFbeta1 levels were similar in affected and unaffected subjects, but concentrations of active TGFbeta1 in conditioned medium of osteoclast cultures was higher in the three CED patients than in the unaffected family member. We concluded that the R218C mutation increases TGFbeta1 bioactivity and enhances osteoclast formation in vitro. The activation of osteoclast activity noted here is consistent with clinical reports that have shown biochemical evidence of increased bone resorption as well as bone formation in CED. | A mutation affecting the /"latency-associated peptide"/ of /"TGFbeta1"/ in /"Camurati-Engelmann disease"/ enhances osteoclast formation in vitro. | /"Camurati-Engelmann disease"/ (/"CED"/) is a rare autosomal dominant disorder characterized by bone pain and osteosclerosis affecting the diaphysis of long bones. /"CED"/ is caused by various missense mutations in the /"TGFB1"/ gene that encodes /"TGFbeta1"/, the most common of which is an arginine-cysteine amino acid change at codon 218 (R218C) in the /"latency-associated peptide"/ domain of /"TGFbeta1"/. We studied osteoclast formation in vitro from peripheral blood mononuclear cells obtained from three related /"CED"/ patients harboring the R218C mutation, in comparison with one family-based and several unrelated controls. Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in /"CED"/ patients, and the increase in osteoclast formation was inhibited by soluble TGFbeta type II receptor. Total serum /"TGFbeta1"/ levels were similar in affected and unaffected subjects, but concentrations of active /"TGFbeta1"/ in conditioned medium of osteoclast cultures was higher in the three /"CED"/ patients than in the unaffected family member. We concluded that the R218C mutation increases /"TGFbeta1"/ bioactivity and enhances osteoclast formation in vitro. The activation of osteoclast activity noted here is consistent with clinical reports that have shown biochemical evidence of increased bone resorption as well as bone formation in /"CED"/. | [
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12843182 | A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro. | Camurati-Engelmann disease (CED) is a rare autosomal dominant disorder characterized by bone pain and osteosclerosis affecting the diaphysis of long bones. CED is caused by various missense mutations in the TGFB1 gene that encodes TGFbeta1, the most common of which is an arginine-cysteine amino acid change at codon 218 (R218C) in the latency-associated peptide domain of TGFbeta1. We studied osteoclast formation in vitro from peripheral blood mononuclear cells obtained from three related CED patients harboring the R218C mutation, in comparison with one family-based and several unrelated controls. Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in CED patients, and the increase in osteoclast formation was inhibited by soluble TGFbeta type II receptor. Total serum TGFbeta1 levels were similar in affected and unaffected subjects, but concentrations of active TGFbeta1 in conditioned medium of osteoclast cultures was higher in the three CED patients than in the unaffected family member. We concluded that the R218C mutation increases TGFbeta1 bioactivity and enhances osteoclast formation in vitro. The activation of osteoclast activity noted here is consistent with clinical reports that have shown biochemical evidence of increased bone resorption as well as bone formation in CED. | A mutation affecting the latency-associated peptide of TGFbeta1 in Camurati-Engelmann disease enhances osteoclast formation in vitro. | Camurati-Engelmann disease (CED) is a rare /"autosomal dominant disorder"/ characterized by bone pain and osteosclerosis affecting the diaphysis of long bones. CED is caused by various missense mutations in the TGFB1 gene that encodes TGFbeta1, the most common of which is an arginine-cysteine amino acid change at codon 218 (R218C) in the latency-associated peptide domain of TGFbeta1. We studied osteoclast formation in vitro from peripheral blood mononuclear cells obtained from three related CED patients harboring the R218C mutation, in comparison with one family-based and several unrelated controls. Osteoclast formation was enhanced approximately 5-fold (P < 0.001) and bone resorption approximately 10-fold (P < 0.001) in CED patients, and the increase in osteoclast formation was inhibited by soluble /"TGFbeta type II receptor"/. Total serum TGFbeta1 levels were similar in affected and unaffected subjects, but concentrations of active TGFbeta1 in conditioned medium of osteoclast cultures was higher in the three CED patients than in the unaffected family member. We concluded that the R218C mutation increases TGFbeta1 bioactivity and enhances osteoclast formation in vitro. The activation of osteoclast activity noted here is consistent with clinical reports that have shown biochemical evidence of increased bone resorption as well as bone formation in CED. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with /"thalassemia"/ intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with /"thalassemia"/ intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with /"thalassemia"/ intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with /"thalassemia"/ intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with thalassemia intermedia and sickle cell disease. | /"Gilbert's syndrome"/ is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in /"Gilbert's syndrome"/. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of /"Gilbert's syndrome"/ in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with thalassemia intermedia and /"sickle cell disease"/. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and /"sickle cell disease"/ considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and /"sickle cell anemia"/. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and /"sickle cell disease"/ may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive /"hemolysis"/ in these patients. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated /"hyperbilirubinemia"/. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | [
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12850481 | Analysis of the A(TA)(n)TAA configuration in the promoter region of the UGT1 A1 gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the UGT1 A1 gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for beta thalassemia and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | Analysis of the A(TA)(n)TAA configuration in the promoter region of the /"UGT1 A1"/ gene in Greek patients with thalassemia intermedia and sickle cell disease. | Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The molecular basis of this syndrome usually concerns an additional dinucleotide insertion (TA) in the A(TA)(n)TAA configuration residing in the promoter region of the /"UGT1 A1"/ gene. This configuration may vary in length; the "n" represents the different number of TA repeats. The homozygosity A(TA)(7)TAA/A(TA)(7)TAA is involved in Gilbert's syndrome. In many cases of patients with thalassemia intermedia and sickle cell disease considerable variation in bilirubin levels is observed. In this study we investigated the contribution of the A(TA)(7)TAA/A(TA)(7)TAA genotype in the variable unconjugated serum bilirubin levels in 31 Greek patients with thalassemia intermedia and 27 Greek compound heterozygotes for /"beta thalassemia"/ and sickle cell anemia. Analysis of the A(TA)(n)TAA configuration in the promoter region of the latter patients showed that those who were carrying the homozygosity A(TA)(7)TAA/A(TA)(7)TAA had higher levels of unconjugated bilirubin. These findings suggest that the coexistence of Gilbert's syndrome in patients with thalassemia intermedia and sickle cell disease may be the cause of the elevated values of unconjugated bilirubin, reducing the possibility of excessive hemolysis in these patients. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( /"GSTT1"/), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for /"atherosclerosis"/, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the /"GSTT1"/-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the /"GSTT1"/-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and /"GSTT1"/ genes was significantly increased ( P=0.008). This study suggests that the /"GSTT1"/-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | /"Glutathione S-transferase M1"/, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of /"glutathione S-transferase M1"/ ( /"GSTM1"/), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for /"atherosclerosis"/, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive /"GSTM1"//T1 genotype, IMT in those with concurrent lack of the /"GSTM1"/ and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( /"GSTP1"/, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for /"atherosclerosis"/, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | /"Glutathione S-transferase M1"/, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of /"glutathione S-transferase M1"/ ( /"GSTM1"/), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean /"intima-media thickness"/ (/"IMT"/) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater /"IMT"/ ( P<0.05). On univariate analysis, carotid /"IMT"/ was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive /"GSTM1"//T1 genotype, /"IMT"/ in those with concurrent lack of the /"GSTM1"/ and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | /"Glutathione S-transferase M1"/, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with /"rheumatoid arthritis"/. | We assessed the contribution of genetic polymorphisms of /"glutathione S-transferase M1"/ ( /"GSTM1"/), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal /"rheumatoid arthritic"/ (/"RA"/) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, /"RA"/ outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive /"GSTM1"//T1 genotype, IMT in those with concurrent lack of the /"GSTM1"/ and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to /"RA"/ in Korean postmenopausal /"RA"/ women without histories of smoking. | [
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12879272 | Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis. | We assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 ( GSTM1), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking. | /"Glutathione S-transferase M1"/, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with /"rheumatoid arthritis"/. | We assessed the contribution of genetic polymorphisms of /"glutathione S-transferase M1"/ ( /"GSTM1"/), T1 ( GSTT1), and P1 ( GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal /"rheumatoid arthritic"/ (/"RA"/) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, /"RA"/ outcomes, and markers of inflammation. Subjects with the GSTT1-0 genotype had greater IMT ( P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1-0 genotype ( P<0.05). When compared to subjects with a double-positive /"GSTM1"//T1 genotype, IMT in those with concurrent lack of the /"GSTM1"/ and GSTT1 genes was significantly increased ( P=0.008). This study suggests that the GSTT1-0 genotype might have an interaction with carotid atherosclerosis related to /"RA"/ in Korean postmenopausal /"RA"/ women without histories of smoking. | [
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12880539 | Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India. | OBJECTIVES: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of apolipoprotein E (apo E) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of apo E gene polymorphisms in premature MI patients and their relation to serum lipid levels. DESIGN AND METHODS: Apo E gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. RESULTS: Higher frequencies of the apo E4 allele (P<0.0001) and of genotypes E3/E4 (P<0.005) and E4/E4 (P<0.005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45.7 (4.9-421.3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8.7 (0.9-86.6)] and those with a high waist : hip ratio [OR (95% CI): 5.6 (1.4-21.2)]. CONCLUSION: Based on the robust association, the apo E4 allele should be considered as an independent risk factor for premature MI in Asian Indians. | /"Apolipoprotein E"/ gene polymorphisms in patients with premature /"myocardial infarction"/: a case-controlled study in Asian Indians in North India. | OBJECTIVES: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of /"apolipoprotein E"/ (/"apo E"/) gene polymorphisms in premature /"myocardial infarction"/ (MI) in this population. This study aimed to study the role of /"apo E"/ gene polymorphisms in premature MI patients and their relation to serum lipid levels. DESIGN AND METHODS: /"Apo E"/ gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. RESULTS: Higher frequencies of the /"apo E4"/ allele (P<0.0001) and of genotypes E3/E4 (P<0.005) and E4/E4 (P<0.005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45.7 (4.9-421.3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8.7 (0.9-86.6)] and those with a high waist : hip ratio [OR (95% CI): 5.6 (1.4-21.2)]. CONCLUSION: Based on the robust association, the /"apo E4"/ allele should be considered as an independent risk factor for premature MI in Asian Indians. | [
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12880539 | Apolipoprotein E gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India. | OBJECTIVES: Several factors, including abdominal obesity, insulin resistance, diabetes mellitus and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of apolipoprotein E (apo E) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of apo E gene polymorphisms in premature MI patients and their relation to serum lipid levels. DESIGN AND METHODS: Apo E gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. RESULTS: Higher frequencies of the apo E4 allele (P<0.0001) and of genotypes E3/E4 (P<0.005) and E4/E4 (P<0.005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45.7 (4.9-421.3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8.7 (0.9-86.6)] and those with a high waist : hip ratio [OR (95% CI): 5.6 (1.4-21.2)]. CONCLUSION: Based on the robust association, the apo E4 allele should be considered as an independent risk factor for premature MI in Asian Indians. | /"Apolipoprotein E"/ gene polymorphisms in patients with premature myocardial infarction: a case-controlled study in Asian Indians in North India. | OBJECTIVES: Several factors, including abdominal obesity, insulin resistance, /"diabetes mellitus"/ and low levels of high-density lipoprotein cholesterol have been implicated in the high prevalence and early onset of coronary heart disease in Asian Indians. However, there are no reports regarding the role of /"apolipoprotein E"/ (/"apo E"/) gene polymorphisms in premature myocardial infarction (MI) in this population. This study aimed to study the role of /"apo E"/ gene polymorphisms in premature MI patients and their relation to serum lipid levels. DESIGN AND METHODS: /"Apo E"/ gene polymorphisms were analysed in 35 patients with MI aged <40 years and in 45 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Levels of serum lipids were measured in addition to the evaluation of conventional risk factors. RESULTS: Higher frequencies of the /"apo E4"/ allele (P<0.0001) and of genotypes E3/E4 (P<0.005) and E4/E4 (P<0.005) were recorded in the premature MI group compared with the controls. Multivariate regression analysis revealed that, after adjusting for other covariates, individuals with the E4 allele were at ~46 times higher odds to develop premature MI compared with individuals without the E4 allele [adjusted odds ratio, OR (95% confidence interval, CI): 45.7 (4.9-421.3)]. Among conventional risk factors, higher risk was observed in those having dyslipidaemia [OR (95% CI): 8.7 (0.9-86.6)] and those with a high waist : hip ratio [OR (95% CI): 5.6 (1.4-21.2)]. CONCLUSION: Based on the robust association, the /"apo E4"/ allele should be considered as an independent risk factor for premature MI in Asian Indians. | [
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12888635 | Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism. | Interindividual differences in the response to dietary intake are, in some cases, genotype dependent. Moreover, genotype-environment interactions may appear when the impact of lifestyle factors (e.g., diet) on a phenotype (e.g., BMI > 30 kg/m(2)) differs by genotype. A case-control study (obese subjects vs. normal weight controls) was conducted to assess a possible effect modification on obesity risk of the Gln27Glu polymorphism for the beta(2)-adrenoceptor gene depending on dietary intake. The sample included 159 subjects with BMI > 30 kg/m(2) and 154 controls with BMI < 25 kg/m(2). The allele frequency for the Glu27 polymorphism, as assessed by the polymerase chain reaction-restriction fragment length polymorphism methodology, was 0.40 in cases (obese) and 0.37 in controls (lean), which was similar to that of other Caucasian populations. The dietary intake was estimated by using a previously validated food frequency questionnaire. Obesity incidence was not directly affected by the polymorphism [odds ratio (OR) = 1.40; P = 0.246]. However, a significant interaction (effect modification) between carbohydrate (CHO) intake and the presence of the Glu27 variant in the probability of obesity was apparent. Thus, females with the polymorphism and a higher CHO intake [>49% energy (E)] had a higher obesity risk (OR = 2.56, P = 0.051). The product-term introduced in the logistic model to assess effect modification revealed a marginally significant interaction (P = 0.058) between both factors. Furthermore, a high intake of CHO (E > 49%) was associated with higher insulin levels among women carrying the Gln27Glu polymorphism (P < 0.01). This gene-nutrient interaction emphasizes the importance of examining the outcome of some obesity-related mutations depending on lifestyle (including diet) and may explain the heterogeneity of findings from previous studies. | Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu /"beta2-adrenoceptor"/ polymorphism. | Interindividual differences in the response to dietary intake are, in some cases, genotype dependent. Moreover, genotype-environment interactions may appear when the impact of lifestyle factors (e.g., diet) on a phenotype (e.g., BMI > 30 kg/m(2)) differs by genotype. A case-control study (/"obese"/ subjects vs. normal weight controls) was conducted to assess a possible effect modification on /"obesity"/ risk of the Gln27Glu polymorphism for the /"beta(2)-adrenoceptor"/ gene depending on dietary intake. The sample included 159 subjects with BMI > 30 kg/m(2) and 154 controls with BMI < 25 kg/m(2). The allele frequency for the Glu27 polymorphism, as assessed by the polymerase chain reaction-restriction fragment length polymorphism methodology, was 0.40 in cases (/"obese"/) and 0.37 in controls (lean), which was similar to that of other Caucasian populations. The dietary intake was estimated by using a previously validated food frequency questionnaire. Obesity incidence was not directly affected by the polymorphism [odds ratio (OR) = 1.40; P = 0.246]. However, a significant interaction (effect modification) between carbohydrate (CHO) intake and the presence of the Glu27 variant in the probability of /"obesity"/ was apparent. Thus, females with the polymorphism and a higher CHO intake [>49% energy (E)] had a higher /"obesity"/ risk (OR = 2.56, P = 0.051). The product-term introduced in the logistic model to assess effect modification revealed a marginally significant interaction (P = 0.058) between both factors. Furthermore, a high intake of CHO (E > 49%) was associated with higher insulin levels among women carrying the Gln27Glu polymorphism (P < 0.01). This gene-nutrient interaction emphasizes the importance of examining the outcome of some /"obesity"/-related mutations depending on lifestyle (including diet) and may explain the heterogeneity of findings from previous studies. | [
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12907273 | Paroxysmal movement disorders in severe myoclonic epilepsy in infancy. | We report on the electroclinical findings and the results of a molecular genetic study of a patient with typical severe myoclonic epilepsy in infancy (TSME) and three with borderline SME (BSME) who showed paroxysmal movement disorders, such as choreoathetosis, dystonia and ballismus, during their clinical course. BSME was defined as a clinical entity that shares common characteristics with TSME but lacks myoclonic seizures associated with ictal EEG changes. When the paroxysmal movement disorders were first observed, all the patients in this study were being treated with polytherapy including phenytoin (PHT), and these abnormal movements disappeared when PHT was discontinued or reduced. However, on other occasions, two of our cases also showed the same abnormal movements even when not being treated with PHT. One patient with TSME and two of the three patients with BSME had SCN1A gene mutations that lead to truncation of the associated protein. We conclude that paroxysmal movement disorders seen in SME patients were closely related to their AED therapy, especially the use of PHT. It is thought that patients with both TSME and BSME have some predisposition toward paroxysmal movement disorders, and that this predisposition is partly related to sodium channel dysfunction, although some other factors might influence the occurrence of this phenomenon. | /"Paroxysmal movement disorders"/ in severe myoclonic epilepsy in infancy. | We report on the electroclinical findings and the results of a molecular genetic study of a patient with typical severe myoclonic epilepsy in infancy (TSME) and three with borderline SME (BSME) who showed /"paroxysmal movement disorders"/, such as choreoathetosis, dystonia and ballismus, during their clinical course. BSME was defined as a clinical entity that shares common characteristics with TSME but lacks myoclonic seizures associated with ictal EEG changes. When the /"paroxysmal movement disorders"/ were first observed, all the patients in this study were being treated with polytherapy including phenytoin (PHT), and these abnormal movements disappeared when PHT was discontinued or reduced. However, on other occasions, two of our cases also showed the same abnormal movements even when not being treated with PHT. One patient with TSME and two of the three patients with BSME had /"SCN1A"/ gene mutations that lead to truncation of the associated protein. We conclude that /"paroxysmal movement disorders"/ seen in SME patients were closely related to their AED therapy, especially the use of PHT. It is thought that patients with both TSME and BSME have some predisposition toward /"paroxysmal movement disorders"/, and that this predisposition is partly related to sodium channel dysfunction, although some other factors might influence the occurrence of this phenomenon. | [
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12907273 | Paroxysmal movement disorders in severe myoclonic epilepsy in infancy. | We report on the electroclinical findings and the results of a molecular genetic study of a patient with typical severe myoclonic epilepsy in infancy (TSME) and three with borderline SME (BSME) who showed paroxysmal movement disorders, such as choreoathetosis, dystonia and ballismus, during their clinical course. BSME was defined as a clinical entity that shares common characteristics with TSME but lacks myoclonic seizures associated with ictal EEG changes. When the paroxysmal movement disorders were first observed, all the patients in this study were being treated with polytherapy including phenytoin (PHT), and these abnormal movements disappeared when PHT was discontinued or reduced. However, on other occasions, two of our cases also showed the same abnormal movements even when not being treated with PHT. One patient with TSME and two of the three patients with BSME had SCN1A gene mutations that lead to truncation of the associated protein. We conclude that paroxysmal movement disorders seen in SME patients were closely related to their AED therapy, especially the use of PHT. It is thought that patients with both TSME and BSME have some predisposition toward paroxysmal movement disorders, and that this predisposition is partly related to sodium channel dysfunction, although some other factors might influence the occurrence of this phenomenon. | Paroxysmal movement disorders in severe myoclonic epilepsy in infancy. | We report on the electroclinical findings and the results of a molecular genetic study of a patient with typical severe myoclonic epilepsy in infancy (TSME) and three with borderline SME (BSME) who showed paroxysmal movement disorders, such as /"choreoathetosis"/, dystonia and ballismus, during their clinical course. BSME was defined as a clinical entity that shares common characteristics with TSME but lacks myoclonic seizures associated with ictal EEG changes. When the paroxysmal movement disorders were first observed, all the patients in this study were being treated with polytherapy including phenytoin (PHT), and these abnormal movements disappeared when PHT was discontinued or reduced. However, on other occasions, two of our cases also showed the same abnormal movements even when not being treated with PHT. One patient with TSME and two of the three patients with BSME had /"SCN1A"/ gene mutations that lead to truncation of the associated protein. We conclude that paroxysmal movement disorders seen in SME patients were closely related to their AED therapy, especially the use of PHT. It is thought that patients with both TSME and BSME have some predisposition toward paroxysmal movement disorders, and that this predisposition is partly related to sodium channel dysfunction, although some other factors might influence the occurrence of this phenomenon. | [
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} | No |
12913211 | Strong association of the Saitohin gene Q7 variant with progressive supranuclear palsy. | Recent reports are inconclusive in showing that the Q7R polymorphism of the novel Saitohin gene, nested in intron 9 of the tau gene, is associated with AD. The authors show that this polymorphism is in complete linkage disequilibrium with the extended tau H1/H2 haplotype and that the Q variant and QQ genotype of Q7R are strongly associated with progressive supranuclear palsy, implicating it as a possibly important pathogenic candidate. | Strong association of the /"Saitohin"/ gene Q7 variant with /"progressive supranuclear palsy"/. | Recent reports are inconclusive in showing that the Q7R polymorphism of the novel /"Saitohin"/ gene, nested in intron 9 of the tau gene, is associated with AD. The authors show that this polymorphism is in complete linkage disequilibrium with the extended tau H1/H2 haplotype and that the Q variant and QQ genotype of Q7R are strongly associated with /"progressive supranuclear palsy"/, implicating it as a possibly important pathogenic candidate. | [
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12913211 | Strong association of the Saitohin gene Q7 variant with progressive supranuclear palsy. | Recent reports are inconclusive in showing that the Q7R polymorphism of the novel Saitohin gene, nested in intron 9 of the tau gene, is associated with AD. The authors show that this polymorphism is in complete linkage disequilibrium with the extended tau H1/H2 haplotype and that the Q variant and QQ genotype of Q7R are strongly associated with progressive supranuclear palsy, implicating it as a possibly important pathogenic candidate. | Strong association of the /"Saitohin"/ gene Q7 variant with progressive supranuclear palsy. | Recent reports are inconclusive in showing that the Q7R polymorphism of the novel /"Saitohin"/ gene, nested in intron 9 of the tau gene, is associated with /"AD"/. The authors show that this polymorphism is in complete linkage disequilibrium with the extended tau H1/H2 haplotype and that the Q variant and QQ genotype of Q7R are strongly associated with progressive supranuclear palsy, implicating it as a possibly important pathogenic candidate. | [
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12915675 | Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism. | Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different MPO genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in atherosclerotic diseases. | Effect of long-term hormone replacement therapy on /"atherosclerosis"/ progression in postmenopausal women relates to /"myeloperoxidase"/ promoter polymorphism. | /"Myeloperoxidase"/ (/"MPO"/) is an oxidative enzyme present in phagocytes and /"atherosclerotic lesions"/. The /"MPO"/ gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of /"atherosclerosis"/ in a 5-yr follow-up study of postmenopausal women with different /"MPO"/ genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The /"atherosclerosis"/ severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the /"MPO"/ genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on /"atherosclerosis"/ progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in /"atherosclerotic diseases"/. | [
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} | Yes |
12915675 | Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism. | Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different MPO genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of HRT. The HRT-EVP group (n = 25) used sequential estradiol valerate plus progestin, the HRT-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no HRT. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the MPO genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the HRT group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and HRT. The effects of HRT on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without HRT. These results may help us understand in greater detail the benefit and possible risk of HRT in atherosclerotic diseases. | Effect of long-term /"hormone replacement therapy"/ on atherosclerosis progression in postmenopausal women relates to /"myeloperoxidase"/ promoter polymorphism. | /"Myeloperoxidase"/ (/"MPO"/) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The /"MPO"/ gene has a promoter polymorphism -463G/A, which leads to high (GG) and low expression (AG, AA) genotypes. We investigated the effect of long-term /"hormone replacement therapy"/ (/"HRT"/) on the progression of atherosclerosis in a 5-yr follow-up study of postmenopausal women with different /"MPO"/ genotypes. Eighty-seven nonsmoking postmenopausal women, aged 45-71 yr, were divided into three groups based on the use of /"HRT"/. The /"HRT"/-EVP group (n = 25) used sequential estradiol valerate plus progestin, the /"HRT"/-EV group used estradiol valerate alone (n = 32), and the control group (n = 30) used no /"HRT"/. The atherosclerosis severity score (ASC) for abdominal aorta and carotid arteries was determined by ultrasonography, and the /"MPO"/ genotype was analyzed. In subjects with the GG genotype, the progression of ASC was significantly faster in the control group than in the /"HRT"/ group (genotype by time interaction, P = 0.042), whereas in A allele carriers there were no significant differences in ASC progression between control and /"HRT"/. The effects of /"HRT"/ on atherosclerosis progression in subjects with the GG genotype seem to be especially beneficial compared with controls with the same genotype but without /"HRT"/. These results may help us understand in greater detail the benefit and possible risk of /"HRT"/ in atherosclerotic diseases. | [
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12918850 | Association between fibrillin-1 gene exon 15 and 27 polymorphisms and risk of mitral valve prolapse. | BACKGROUND AND AIM OF THE STUDY: Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. Abnormalities of elastic fiber were found in floppy mitral valves. The role of fibrillin genetic variant in isolated mitral valve prolapse (MVP) has not been studied. Hence, a case-controlled study was performed to investigate the relationship between fibrillin-1 gene polymorphisms and risk of MVP in Taiwan Chinese. METHODS: One hundred patients with MVP diagnosed by echocardiography and 140 age- and sex-matched normal controls were studied. Polymorphisms of exon 15, 27 and intron C of the fibrillin-1 gene (FBN1) were identified by polymerase chain reaction-based restriction analysis. RESULTS: A significant difference was seen in genotype distribution or allelic frequency between MVP cases and controls for either FBN1 exon 15 polymorphism (p = 0.012 and 0.002, respectively) or exon 27 polymorphism (p = 0.04 and 0.02, respectively). Odds ratios (OR) for risk of MVP associated with FBN1 exon 15 TT and exon 27 GG genotypes were 2.40 (95% CI 1.32-4.39) and 3.61 (95% CI 1.01-12.89), respectively. OR for risk of MVP associated with FBN1 exon 15 T and exon 27 G alleles were 2.24 (95% CI 1.32-3.81) and 1.66 (95% CI 1.07-2.56), respectively. There was no significant difference in the distribution of FBN1 intron C genotypes (p = 0.58) and allelic frequency (p = 0.34) between MVP cases and controls. CONCLUSION: Patients with MVP have higher frequencies of FBN1 exon 15 TT and exon 27 GG genotypes, which supports a role of the FBN1 exon 15 and 27 polymorphisms in determining the risk of MVP among the Chinese population in Taiwan. | Association between /"fibrillin-1"/ gene exon 15 and 27 polymorphisms and risk of /"mitral valve prolapse"/. | BACKGROUND AND AIM OF THE STUDY: Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. Abnormalities of elastic fiber were found in /"floppy mitral valves"/. The role of fibrillin genetic variant in isolated /"mitral valve prolapse"/ (/"MVP"/) has not been studied. Hence, a case-controlled study was performed to investigate the relationship between /"fibrillin-1"/ gene polymorphisms and risk of /"MVP"/ in Taiwan Chinese. METHODS: One hundred patients with /"MVP"/ diagnosed by echocardiography and 140 age- and sex-matched normal controls were studied. Polymorphisms of exon 15, 27 and intron C of the /"fibrillin-1"/ gene (/"FBN1"/) were identified by polymerase chain reaction-based restriction analysis. RESULTS: A significant difference was seen in genotype distribution or allelic frequency between /"MVP"/ cases and controls for either /"FBN1"/ exon 15 polymorphism (p = 0.012 and 0.002, respectively) or exon 27 polymorphism (p = 0.04 and 0.02, respectively). Odds ratios (OR) for risk of /"MVP"/ associated with /"FBN1"/ exon 15 TT and exon 27 GG genotypes were 2.40 (95% CI 1.32-4.39) and 3.61 (95% CI 1.01-12.89), respectively. OR for risk of /"MVP"/ associated with /"FBN1"/ exon 15 T and exon 27 G alleles were 2.24 (95% CI 1.32-3.81) and 1.66 (95% CI 1.07-2.56), respectively. There was no significant difference in the distribution of /"FBN1"/ intron C genotypes (p = 0.58) and allelic frequency (p = 0.34) between /"MVP"/ cases and controls. CONCLUSION: Patients with /"MVP"/ have higher frequencies of /"FBN1"/ exon 15 TT and exon 27 GG genotypes, which supports a role of the /"FBN1"/ exon 15 and 27 polymorphisms in determining the risk of /"MVP"/ among the Chinese population in Taiwan. | [
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"entity_id": "D008945",
"entity_type": "Disease",
"text_name": "mitral valve prolapse"
} | Yes |
12918850 | Association between fibrillin-1 gene exon 15 and 27 polymorphisms and risk of mitral valve prolapse. | BACKGROUND AND AIM OF THE STUDY: Fibrillin is one of the structural components of the elastin-associated microfibrils found in the mitral valve. Abnormalities of elastic fiber were found in floppy mitral valves. The role of fibrillin genetic variant in isolated mitral valve prolapse (MVP) has not been studied. Hence, a case-controlled study was performed to investigate the relationship between fibrillin-1 gene polymorphisms and risk of MVP in Taiwan Chinese. METHODS: One hundred patients with MVP diagnosed by echocardiography and 140 age- and sex-matched normal controls were studied. Polymorphisms of exon 15, 27 and intron C of the fibrillin-1 gene (FBN1) were identified by polymerase chain reaction-based restriction analysis. RESULTS: A significant difference was seen in genotype distribution or allelic frequency between MVP cases and controls for either FBN1 exon 15 polymorphism (p = 0.012 and 0.002, respectively) or exon 27 polymorphism (p = 0.04 and 0.02, respectively). Odds ratios (OR) for risk of MVP associated with FBN1 exon 15 TT and exon 27 GG genotypes were 2.40 (95% CI 1.32-4.39) and 3.61 (95% CI 1.01-12.89), respectively. OR for risk of MVP associated with FBN1 exon 15 T and exon 27 G alleles were 2.24 (95% CI 1.32-3.81) and 1.66 (95% CI 1.07-2.56), respectively. There was no significant difference in the distribution of FBN1 intron C genotypes (p = 0.58) and allelic frequency (p = 0.34) between MVP cases and controls. CONCLUSION: Patients with MVP have higher frequencies of FBN1 exon 15 TT and exon 27 GG genotypes, which supports a role of the FBN1 exon 15 and 27 polymorphisms in determining the risk of MVP among the Chinese population in Taiwan. | Association between fibrillin-1 gene exon 15 and 27 polymorphisms and risk of /"mitral valve prolapse"/. | BACKGROUND AND AIM OF THE STUDY: Fibrillin is one of the structural components of the /"elastin"/-associated microfibrils found in the mitral valve. Abnormalities of elastic fiber were found in /"floppy mitral valves"/. The role of fibrillin genetic variant in isolated /"mitral valve prolapse"/ (/"MVP"/) has not been studied. Hence, a case-controlled study was performed to investigate the relationship between fibrillin-1 gene polymorphisms and risk of /"MVP"/ in Taiwan Chinese. METHODS: One hundred patients with /"MVP"/ diagnosed by echocardiography and 140 age- and sex-matched normal controls were studied. Polymorphisms of exon 15, 27 and intron C of the fibrillin-1 gene (FBN1) were identified by polymerase chain reaction-based restriction analysis. RESULTS: A significant difference was seen in genotype distribution or allelic frequency between /"MVP"/ cases and controls for either FBN1 exon 15 polymorphism (p = 0.012 and 0.002, respectively) or exon 27 polymorphism (p = 0.04 and 0.02, respectively). Odds ratios (OR) for risk of /"MVP"/ associated with FBN1 exon 15 TT and exon 27 GG genotypes were 2.40 (95% CI 1.32-4.39) and 3.61 (95% CI 1.01-12.89), respectively. OR for risk of /"MVP"/ associated with FBN1 exon 15 T and exon 27 G alleles were 2.24 (95% CI 1.32-3.81) and 1.66 (95% CI 1.07-2.56), respectively. There was no significant difference in the distribution of FBN1 intron C genotypes (p = 0.58) and allelic frequency (p = 0.34) between /"MVP"/ cases and controls. CONCLUSION: Patients with /"MVP"/ have higher frequencies of FBN1 exon 15 TT and exon 27 GG genotypes, which supports a role of the FBN1 exon 15 and 27 polymorphisms in determining the risk of /"MVP"/ among the Chinese population in Taiwan. | [
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"entity_id": "D008945",
"entity_type": "Disease",
"text_name": "floppy mitral valves"
} | No |
12928282 | Clinical features of X linked juvenile retinoschisis associated with new mutations in the XLRS1 gene in Italian families. | AIMS: To describe the clinical phenotype of X linked juvenile retinoschisis in eight Italian families with six different mutations in the XLRS1 gene. METHODS: Complete ophthalmic examinations, electroretinography and A and B-scan standardised echography were performed in 18 affected males. The coding sequences of the XLRS1 gene were amplified by polymerase chain reaction and directly sequenced on an automated sequencer. RESULTS: Six different XLRS1 mutations were identified; two of these mutations Ile81Asn and the Trp122Cys, have not been previously described. The affected males showed an electronegative response to the standard white scotopic stimulus and a prolonged implicit time of the 30 Hz flicker. In the families with Trp112Cys and Trp122Cys mutations we observed a more severe retinoschisis (RS) clinical picture compared with the other genotypes. CONCLUSION: The severe RS phenotypes associated with Trp112Cys and to Trp122Cys mutations suggest that these mutations determine a notable alteration in the function of the retinoschisin protein. | Clinical features of /"X linked juvenile retinoschisis"/ associated with new mutations in the /"XLRS1"/ gene in Italian families. | AIMS: To describe the clinical phenotype of /"X linked juvenile retinoschisis"/ in eight Italian families with six different mutations in the /"XLRS1"/ gene. METHODS: Complete ophthalmic examinations, electroretinography and A and B-scan standardised echography were performed in 18 affected males. The coding sequences of the /"XLRS1"/ gene were amplified by polymerase chain reaction and directly sequenced on an automated sequencer. RESULTS: Six different /"XLRS1"/ mutations were identified; two of these mutations Ile81Asn and the Trp122Cys, have not been previously described. The affected males showed an electronegative response to the standard white scotopic stimulus and a prolonged implicit time of the 30 Hz flicker. In the families with Trp112Cys and Trp122Cys mutations we observed a more severe /"retinoschisis"/ (/"RS"/) clinical picture compared with the other genotypes. CONCLUSION: The severe /"RS"/ phenotypes associated with Trp112Cys and to Trp122Cys mutations suggest that these mutations determine a notable alteration in the function of the /"retinoschisin"/ protein. | [
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} | {
"begin_idx": "21",
"end_idx": "52",
"entity_id": "D041441",
"entity_type": "Disease",
"text_name": "X linked juvenile retinoschisis"
} | Yes |
12928685 | Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion. | PURPOSE: Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between factor V Leiden, prothrombin 20210A, and retinal artery occlusion. METHODS: In the present retrospective case-control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of factor V Leiden and prothrombin 20210A alleles was determined by polymerase chain reaction. RESULTS: The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of factor V Leiden genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls. CONCLUSION: Our data suggest that factor V Leiden and prothrombin 20210A do not play a major role in patients with retinal artery occlusion. | Role of /"factor V Leiden"/ and prothrombin 20210A in patients with /"retinal artery occlusion"/. | PURPOSE: /"retinal artery occlusion"/ is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with /"retinal artery occlusion"/. Numerous studies have shown that two genetic variants, /"factor V Leiden"/ and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of /"retinal artery occlusion"/ is still unclear. The purpose of the present study was therefore to investigate a possible association between /"factor V Leiden"/, prothrombin 20210A, and /"retinal artery occlusion"/. METHODS: In the present retrospective case-control study, we studied 136 patients with /"retinal artery occlusion"/ and 136 age- and gender-matched control subjects. The presence of /"factor V Leiden"/ and prothrombin 20210A alleles was determined by polymerase chain reaction. RESULTS: The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of /"factor V Leiden"/ genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls. CONCLUSION: Our data suggest that /"factor V Leiden"/ and prothrombin 20210A do not play a major role in patients with /"retinal artery occlusion"/. | [
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}
] | {
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"text_name": "factor V Leiden"
} | {
"begin_idx": "64",
"end_idx": "88",
"entity_id": "D015356",
"entity_type": "Disease",
"text_name": "retinal artery occlusion"
} | Yes |
12928685 | Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion. | PURPOSE: Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between factor V Leiden, prothrombin 20210A, and retinal artery occlusion. METHODS: In the present retrospective case-control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of factor V Leiden and prothrombin 20210A alleles was determined by polymerase chain reaction. RESULTS: The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of factor V Leiden genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls. CONCLUSION: Our data suggest that factor V Leiden and prothrombin 20210A do not play a major role in patients with retinal artery occlusion. | Role of /"factor V Leiden"/ and prothrombin 20210A in patients with retinal artery occlusion. | PURPOSE: Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, /"factor V Leiden"/ and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between /"factor V Leiden"/, prothrombin 20210A, and retinal artery occlusion. METHODS: In the present retrospective case-control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of /"factor V Leiden"/ and prothrombin 20210A alleles was determined by polymerase chain reaction. RESULTS: The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of /"factor V Leiden"/ genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and /"myocardial infarction"/ were significantly more frequent in patients than in controls. CONCLUSION: Our data suggest that /"factor V Leiden"/ and prothrombin 20210A do not play a major role in patients with retinal artery occlusion. | [
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} | No |
12930595 | Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins. | Thyrotropin (TSH) receptor (TSHr) mutations have been investigated in relation to Graves' disease (GD) genetic susceptibility under the hypothesis that a modified antigen may have novel immunogenic properties. The prevalence of three germline polymorphisms--D36H, P52T, and D727E--were studied in a cohort of multiracial GD patients together with their associations with disease state, Graves' ophthalmopathy, and thyroid autoantibodies titers. Polymerase chain reaction products of exon 1 and 10e of the TSHr were generated from 164 GD patients (109 Chinese, 34 Malays, and 21 Indians) and 240 individuals with no thyroid illnesses (74 Chinese, 84 Malays, and 82 Indians). Mutations were detected by single-strand conformational polymorphism and confirmed with direct sequencing. The D36H mutation was absent, while significant ethnic differences in the distribution of the P52T and D727E mutations were found. The levels of thyroid autoantibodies also differed significantly amongst the three ethnic groups, with the Indian cohort having the lowest titer. Both the P52T and D727E mutations were not associated with GD. An intron mutation, C/G+63IVS1, was detected and showed significant association with GD. Overall, it conferred a twofold increase risk of GD, while subgroup analysis showed increased odds ratios of 2.4 for Chinese (p = 0.008) and 2.8 for Indian (p = 0.049) but not for the Malay ethnic group. Together with recent identification of disease susceptibility markers in the region of the TSHr gene, these results are supportive of genetic factors existing in this region that may be in linkage disequilibrium with the inheritance of various TSHr polymorphisms. | Association of /"Graves' disease"/ with intragenic polymorphism of the /"thyrotropin receptor"/ gene in a cohort of Singapore patients of multi-ethnic origins. | Thyrotropin (TSH) receptor (/"TSHr"/) mutations have been investigated in relation to /"Graves' disease"/ (/"GD"/) genetic susceptibility under the hypothesis that a modified antigen may have novel immunogenic properties. The prevalence of three germline polymorphisms--D36H, P52T, and D727E--were studied in a cohort of multiracial /"GD"/ patients together with their associations with disease state, Graves' ophthalmopathy, and thyroid autoantibodies titers. Polymerase chain reaction products of exon 1 and 10e of the /"TSHr"/ were generated from 164 /"GD"/ patients (109 Chinese, 34 Malays, and 21 Indians) and 240 individuals with no thyroid illnesses (74 Chinese, 84 Malays, and 82 Indians). Mutations were detected by single-strand conformational polymorphism and confirmed with direct sequencing. The D36H mutation was absent, while significant ethnic differences in the distribution of the P52T and D727E mutations were found. The levels of thyroid autoantibodies also differed significantly amongst the three ethnic groups, with the Indian cohort having the lowest titer. Both the P52T and D727E mutations were not associated with /"GD"/. An intron mutation, C/G+63IVS1, was detected and showed significant association with /"GD"/. Overall, it conferred a twofold increase risk of /"GD"/, while subgroup analysis showed increased odds ratios of 2.4 for Chinese (p = 0.008) and 2.8 for Indian (p = 0.049) but not for the Malay ethnic group. Together with recent identification of disease susceptibility markers in the region of the /"TSHr"/ gene, these results are supportive of genetic factors existing in this region that may be in linkage disequilibrium with the inheritance of various /"TSHr"/ polymorphisms. | [
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} | Yes |
12930595 | Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins. | Thyrotropin (TSH) receptor (TSHr) mutations have been investigated in relation to Graves' disease (GD) genetic susceptibility under the hypothesis that a modified antigen may have novel immunogenic properties. The prevalence of three germline polymorphisms--D36H, P52T, and D727E--were studied in a cohort of multiracial GD patients together with their associations with disease state, Graves' ophthalmopathy, and thyroid autoantibodies titers. Polymerase chain reaction products of exon 1 and 10e of the TSHr were generated from 164 GD patients (109 Chinese, 34 Malays, and 21 Indians) and 240 individuals with no thyroid illnesses (74 Chinese, 84 Malays, and 82 Indians). Mutations were detected by single-strand conformational polymorphism and confirmed with direct sequencing. The D36H mutation was absent, while significant ethnic differences in the distribution of the P52T and D727E mutations were found. The levels of thyroid autoantibodies also differed significantly amongst the three ethnic groups, with the Indian cohort having the lowest titer. Both the P52T and D727E mutations were not associated with GD. An intron mutation, C/G+63IVS1, was detected and showed significant association with GD. Overall, it conferred a twofold increase risk of GD, while subgroup analysis showed increased odds ratios of 2.4 for Chinese (p = 0.008) and 2.8 for Indian (p = 0.049) but not for the Malay ethnic group. Together with recent identification of disease susceptibility markers in the region of the TSHr gene, these results are supportive of genetic factors existing in this region that may be in linkage disequilibrium with the inheritance of various TSHr polymorphisms. | Association of Graves' disease with intragenic polymorphism of the /"thyrotropin receptor"/ gene in a cohort of Singapore patients of multi-ethnic origins. | Thyrotropin (TSH) receptor (/"TSHr"/) mutations have been investigated in relation to Graves' disease (GD) genetic susceptibility under the hypothesis that a modified antigen may have novel immunogenic properties. The prevalence of three germline polymorphisms--D36H, P52T, and D727E--were studied in a cohort of multiracial GD patients together with their associations with disease state, Graves' /"ophthalmopathy"/, and thyroid autoantibodies titers. Polymerase chain reaction products of exon 1 and 10e of the /"TSHr"/ were generated from 164 GD patients (109 Chinese, 34 Malays, and 21 Indians) and 240 individuals with no thyroid illnesses (74 Chinese, 84 Malays, and 82 Indians). Mutations were detected by single-strand conformational polymorphism and confirmed with direct sequencing. The D36H mutation was absent, while significant ethnic differences in the distribution of the P52T and D727E mutations were found. The levels of thyroid autoantibodies also differed significantly amongst the three ethnic groups, with the Indian cohort having the lowest titer. Both the P52T and D727E mutations were not associated with GD. An intron mutation, C/G+63IVS1, was detected and showed significant association with GD. Overall, it conferred a twofold increase risk of GD, while subgroup analysis showed increased odds ratios of 2.4 for Chinese (p = 0.008) and 2.8 for Indian (p = 0.049) but not for the Malay ethnic group. Together with recent identification of disease susceptibility markers in the region of the /"TSHr"/ gene, these results are supportive of genetic factors existing in this region that may be in linkage disequilibrium with the inheritance of various /"TSHr"/ polymorphisms. | [
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"text_name": "TSHr"
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"entity_id": "D049970",
"entity_type": "Disease",
"text_name": "ophthalmopathy"
} | No |
12930688 | [Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [Mutation analysis on /"MSH2"/ and MLH1 genes in patients of /"colorectal cancer"/ at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes /"MSH2"/ and MLH1 in the patients onset of /"colorectal cancers"/ (/"CRC"/) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with /"CRC"/. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in /"MSH2"/ gene and a missense mutation Met242Ile in MLH1 gene were unveiled in /"CRC"/ tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of /"CRC"/ with onset at early ages. | [
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},
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"text_name": "MSI"
},
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"end_idx": "35",
"entity_id": "4292",
"entity_type": "Gene",
"text_name": "MLH1"
},
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"text_name": "MSH2"
},
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"entity_type": "Gene",
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},
{
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"end_idx": "1071",
"entity_id": "4436",
"entity_type": "Gene",
"text_name": "MSH2"
}
] | {
"begin_idx": "22",
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"entity_id": "4436",
"entity_type": "Gene",
"text_name": "MSH2"
} | {
"begin_idx": "241",
"end_idx": "259",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancers"
} | Yes |
12930688 | [Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [Mutation analysis on MSH2 and /"MLH1"/ genes in patients of /"colorectal cancer"/ at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and /"MLH1"/ in the patients onset of /"colorectal cancers"/ (/"CRC"/) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with /"CRC"/. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in /"MLH1"/ gene were unveiled in /"CRC"/ tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of /"CRC"/ with onset at early ages. | [
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},
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},
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},
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},
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"entity_id": "4436",
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}
] | {
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"entity_id": "4292",
"entity_type": "Gene",
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} | {
"begin_idx": "241",
"end_idx": "259",
"entity_id": "D015179",
"entity_type": "Disease",
"text_name": "colorectal cancers"
} | Yes |
12930688 | [Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [Mutation analysis on MSH2 and /"MLH1"/ genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and /"MLH1"/ in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the /"tumor"/ tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in /"MLH1"/ gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [
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"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
} | No |
12930688 | [Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [Mutation analysis on MSH2 and /"MLH1"/ genes in patients of colorectal cancer at early age]. | OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and /"MLH1"/ in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of /"microsatellite instability"/ (/"MSI"/) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with /"MSI"/(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were /"microsatellite instability"/ positive (/"MSI"/(+)), 10/42 /"MSI"/(+)-H and 12/42 /"MSI"/(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with /"MSI"/(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in /"MLH1"/ gene were unveiled in CRC tissues of two patients with /"MSI"/(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages. | [
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"entity_id": "D053842",
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12932609 | Myotrophin in human heart failure. | OBJECTIVES: The goal of this study was to investigate plasma levels of myotrophin in heart failure (HF) and their relationship to gender and disease severity. BACKGROUND: Myotrophin is a myocardial hypertrophy-inducing factor initially demonstrated in hypertrophied and cardiomyopathic hearts. Recent evidence suggests an interaction with the transcription factor nuclear factor kappa B (NFkappaB), which is activated in HF and modulates myocardial protein expression. It is unknown whether this peptide has an endocrine/paracrine role in man. We hypothesized that it may have a role in HF and would be raised in plasma. METHODS: We developed a competitive binding assay specific for human myotrophin. Myotrophin was measured in plasma extracts of 120 HF patients and 130 age- and gender-matched normal controls. RESULTS: Myotrophin in plasma existed as the full-length 12 kD form with also a 2.7 kD form (possibly a degradation product). Log normalized myotrophin levels were significantly elevated in HF patients (mean +/- SEM [geometric mean, range], 2.402 +/- 0.021 [252, 72 to 933] vs. 2.268 +/- 0.021 [185, 28 to 501] fmol/ml, p < 0.0005). There was no relationship between myotrophin and age or gender in controls. However, males with HF had higher levels of myotrophin than females (p < 0.001). There was an inverse relationship of myotrophin levels with New York Heart Association class in patients with no gender difference in the relationship. CONCLUSIONS: There is evidence of early activation of the myotrophin system in HF, which is more evident in males. This response is attenuated in more severe disease. The contribution of myotrophin to NFkappaB-mediated gene transcription and preservation of cardiac muscle mass remains to be investigated further. | /"Myotrophin"/ in human /"heart failure"/. | OBJECTIVES: The goal of this study was to investigate plasma levels of /"myotrophin"/ in /"heart failure"/ (/"HF"/) and their relationship to gender and disease severity. BACKGROUND: /"Myotrophin"/ is a myocardial hypertrophy-inducing factor initially demonstrated in hypertrophied and cardiomyopathic hearts. Recent evidence suggests an interaction with the transcription factor nuclear factor kappa B (NFkappaB), which is activated in /"HF"/ and modulates myocardial protein expression. It is unknown whether this peptide has an endocrine/paracrine role in man. We hypothesized that it may have a role in /"HF"/ and would be raised in plasma. METHODS: We developed a competitive binding assay specific for human /"myotrophin"/. /"Myotrophin"/ was measured in plasma extracts of 120 /"HF"/ patients and 130 age- and gender-matched normal controls. RESULTS: /"Myotrophin"/ in plasma existed as the full-length 12 kD form with also a 2.7 kD form (possibly a degradation product). Log normalized /"myotrophin"/ levels were significantly elevated in /"HF"/ patients (mean +/- SEM [geometric mean, range], 2.402 +/- 0.021 [252, 72 to 933] vs. 2.268 +/- 0.021 [185, 28 to 501] fmol/ml, p < 0.0005). There was no relationship between /"myotrophin"/ and age or gender in controls. However, males with /"HF"/ had higher levels of /"myotrophin"/ than females (p < 0.001). There was an inverse relationship of /"myotrophin"/ levels with New York Heart Association class in patients with no gender difference in the relationship. CONCLUSIONS: There is evidence of early activation of the /"myotrophin"/ system in /"HF"/, which is more evident in males. This response is attenuated in more severe disease. The contribution of /"myotrophin"/ to NFkappaB-mediated gene transcription and preservation of cardiac muscle mass remains to be investigated further. | [
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12932609 | Myotrophin in human heart failure. | OBJECTIVES: The goal of this study was to investigate plasma levels of myotrophin in heart failure (HF) and their relationship to gender and disease severity. BACKGROUND: Myotrophin is a myocardial hypertrophy-inducing factor initially demonstrated in hypertrophied and cardiomyopathic hearts. Recent evidence suggests an interaction with the transcription factor nuclear factor kappa B (NFkappaB), which is activated in HF and modulates myocardial protein expression. It is unknown whether this peptide has an endocrine/paracrine role in man. We hypothesized that it may have a role in HF and would be raised in plasma. METHODS: We developed a competitive binding assay specific for human myotrophin. Myotrophin was measured in plasma extracts of 120 HF patients and 130 age- and gender-matched normal controls. RESULTS: Myotrophin in plasma existed as the full-length 12 kD form with also a 2.7 kD form (possibly a degradation product). Log normalized myotrophin levels were significantly elevated in HF patients (mean +/- SEM [geometric mean, range], 2.402 +/- 0.021 [252, 72 to 933] vs. 2.268 +/- 0.021 [185, 28 to 501] fmol/ml, p < 0.0005). There was no relationship between myotrophin and age or gender in controls. However, males with HF had higher levels of myotrophin than females (p < 0.001). There was an inverse relationship of myotrophin levels with New York Heart Association class in patients with no gender difference in the relationship. CONCLUSIONS: There is evidence of early activation of the myotrophin system in HF, which is more evident in males. This response is attenuated in more severe disease. The contribution of myotrophin to NFkappaB-mediated gene transcription and preservation of cardiac muscle mass remains to be investigated further. | /"Myotrophin"/ in human heart failure. | OBJECTIVES: The goal of this study was to investigate plasma levels of /"myotrophin"/ in heart failure (HF) and their relationship to gender and disease severity. BACKGROUND: /"Myotrophin"/ is a /"myocardial hypertrophy"/-inducing factor initially demonstrated in hypertrophied and cardiomyopathic hearts. Recent evidence suggests an interaction with the transcription factor nuclear factor kappa B (NFkappaB), which is activated in HF and modulates myocardial protein expression. It is unknown whether this peptide has an endocrine/paracrine role in man. We hypothesized that it may have a role in HF and would be raised in plasma. METHODS: We developed a competitive binding assay specific for human /"myotrophin"/. /"Myotrophin"/ was measured in plasma extracts of 120 HF patients and 130 age- and gender-matched normal controls. RESULTS: /"Myotrophin"/ in plasma existed as the full-length 12 kD form with also a 2.7 kD form (possibly a degradation product). Log normalized /"myotrophin"/ levels were significantly elevated in HF patients (mean +/- SEM [geometric mean, range], 2.402 +/- 0.021 [252, 72 to 933] vs. 2.268 +/- 0.021 [185, 28 to 501] fmol/ml, p < 0.0005). There was no relationship between /"myotrophin"/ and age or gender in controls. However, males with HF had higher levels of /"myotrophin"/ than females (p < 0.001). There was an inverse relationship of /"myotrophin"/ levels with New York Heart Association class in patients with no gender difference in the relationship. CONCLUSIONS: There is evidence of early activation of the /"myotrophin"/ system in HF, which is more evident in males. This response is attenuated in more severe disease. The contribution of /"myotrophin"/ to NFkappaB-mediated gene transcription and preservation of cardiac muscle mass remains to be investigated further. | [
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12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | PURPOSE: To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. METHODS: Clinical examination and linkage analysis of both families using markers flanking the COL2A1 gene associated with Stickler syndrome type 1, the loci for Wagner disease/erosive vitreoretinopathy (5q14.3), high myopia (18p11.31 and 12q21-q23), and nonsyndromic congenital retinal nonattachment (10q21). RESULTS: Fifteen individuals from family A and 12 individuals from family B showed RRD or retinal tears with minimal (family A) or no (family B) systemic characteristics of Stickler syndrome and no ocular features of Wagner disease or erosive vitreoretinopathy. The RRD cosegregated fully with a chromosomal region harboring the COL2A1 gene with maximum lod scores of 6.09 (family A) and 4.97 (family B). In family B, an Arg453Ter mutation was identified in exon 30 of the COL2A1 gene, that was previously described in a patient with classic Stickler syndrome. In family A, DNA sequence analysis revealed no mutation in the coding region and at the splice sites of the COL2A1 gene. CONCLUSIONS: In two large families with RRD, linkage was found at the COL2A1 locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of COL2A1 have been associated until now with classic Stickler syndrome. | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the /"COL2A1"/ gene. | PURPOSE: To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (/"RRD"/) in two large families. METHODS: Clinical examination and linkage analysis of both families using markers flanking the /"COL2A1"/ gene associated with Stickler syndrome type 1, the loci for Wagner disease/erosive vitreoretinopathy (5q14.3), high myopia (18p11.31 and 12q21-q23), and nonsyndromic congenital retinal nonattachment (10q21). RESULTS: Fifteen individuals from family A and 12 individuals from family B showed RRD or retinal tears with minimal (family A) or no (family B) systemic characteristics of Stickler syndrome and no ocular features of Wagner disease or erosive vitreoretinopathy. The /"RRD"/ cosegregated fully with a chromosomal region harboring the /"COL2A1"/ gene with maximum lod scores of 6.09 (family A) and 4.97 (family B). In family B, an Arg453Ter mutation was identified in exon 30 of the /"COL2A1"/ gene, that was previously described in a patient with classic Stickler syndrome. In family A, DNA sequence analysis revealed no mutation in the coding region and at the splice sites of the /"COL2A1"/ gene. CONCLUSIONS: In two large families with /"RRD"/, linkage was found at the /"COL2A1"/ locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of /"COL2A1"/ have been associated until now with classic Stickler syndrome. | [
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12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | PURPOSE: To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. METHODS: Clinical examination and linkage analysis of both families using markers flanking the COL2A1 gene associated with Stickler syndrome type 1, the loci for Wagner disease/erosive vitreoretinopathy (5q14.3), high myopia (18p11.31 and 12q21-q23), and nonsyndromic congenital retinal nonattachment (10q21). RESULTS: Fifteen individuals from family A and 12 individuals from family B showed RRD or retinal tears with minimal (family A) or no (family B) systemic characteristics of Stickler syndrome and no ocular features of Wagner disease or erosive vitreoretinopathy. The RRD cosegregated fully with a chromosomal region harboring the COL2A1 gene with maximum lod scores of 6.09 (family A) and 4.97 (family B). In family B, an Arg453Ter mutation was identified in exon 30 of the COL2A1 gene, that was previously described in a patient with classic Stickler syndrome. In family A, DNA sequence analysis revealed no mutation in the coding region and at the splice sites of the COL2A1 gene. CONCLUSIONS: In two large families with RRD, linkage was found at the COL2A1 locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of COL2A1 have been associated until now with classic Stickler syndrome. | /"Autosomal dominant rhegmatogenous retinal detachment"/ associated with an Arg453Ter mutation in the /"COL2A1"/ gene. | PURPOSE: To investigate the clinical features and molecular causes of /"autosomal dominant rhegmatogenous retinal detachment"/ (RRD) in two large families. METHODS: Clinical examination and linkage analysis of both families using markers flanking the /"COL2A1"/ gene associated with Stickler syndrome type 1, the loci for Wagner disease/erosive vitreoretinopathy (5q14.3), high myopia (18p11.31 and 12q21-q23), and nonsyndromic congenital retinal nonattachment (10q21). RESULTS: Fifteen individuals from family A and 12 individuals from family B showed RRD or retinal tears with minimal (family A) or no (family B) systemic characteristics of Stickler syndrome and no ocular features of Wagner disease or erosive vitreoretinopathy. The RRD cosegregated fully with a chromosomal region harboring the /"COL2A1"/ gene with maximum lod scores of 6.09 (family A) and 4.97 (family B). In family B, an Arg453Ter mutation was identified in exon 30 of the /"COL2A1"/ gene, that was previously described in a patient with classic Stickler syndrome. In family A, DNA sequence analysis revealed no mutation in the coding region and at the splice sites of the /"COL2A1"/ gene. CONCLUSIONS: In two large families with RRD, linkage was found at the /"COL2A1"/ locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of /"COL2A1"/ have been associated until now with classic Stickler syndrome. | [
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12939427 | Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians. | Myelin basic protein gene is associated with /"MS"/ in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to /"multiple sclerosis"/ (/"MS"/). The association of /"MS"/ with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible /"MS"/ association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite /"MS"/ and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to /"HLA-DRB1"/ phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both /"MS"/ patients and control subjects, was very similar. When /"MS"/ patients and healthy control subjects were stratified according to /"HLA-DRB1"/ phenotypes, a significant association of /"MS"/ with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of /"MS"/ for the subgroups of DR4- and DR5-positive Italians and Russians. | [
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12939427 | Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians. | /"Myelin basic protein"/ gene is associated with /"MS"/ in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The /"myelin basic protein"/ (/"MBP"/) gene may confer genetic susceptibility to /"multiple sclerosis"/ (/"MS"/). The association of /"MS"/ with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the /"MBP"/ gene is the subject of conflicting reports. OBJECTIVE: To study possible /"MS"/ association with VNTR alleles of /"MBP"/ gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite /"MS"/ and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the /"MBP"/ VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of /"MBP"/ alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of /"MBP"/ alleles and genotypes in the two ethnic groups, including both /"MS"/ patients and control subjects, was very similar. When /"MS"/ patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of /"MS"/ with /"MBP"/ alleles was found only in the DR4- and DR5-positive subgroups. A significant association with /"MBP"/ alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the /"MBP"/ or another gene in its vicinity appears to contribute to the etiology of /"MS"/ for the subgroups of DR4- and DR5-positive Italians and Russians. | [
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12939427 | Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians. | Myelin basic protein gene is associated with MS in /"DR4"/- and DR5-positive Italians and Russians. | BACKGROUND: The /"myelin basic protein"/ (/"MBP"/) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the /"MBP"/ gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of /"MBP"/ gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the /"MBP"/ VNTR region and for the human /"leukocyte antigen (HLA) class II DRB1"/ gene. The phenotype, allele, and genotype frequencies for two groups of /"MBP"/ alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of /"MBP"/ alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with /"MBP"/ alleles was found only in the /"DR4"/- and DR5-positive subgroups. A significant association with /"MBP"/ alleles was also observed in the nonstratified groups, owing mainly to the contribution of the /"DR4"/- and DR5-positive individuals. CONCLUSION: Polymorphism of the /"MBP"/ or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of /"DR4"/- and DR5-positive Italians and Russians. | [
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12939427 | Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians. | Myelin basic protein gene is associated with MS in /"DR4"/- and DR5-positive Italians and Russians. | BACKGROUND: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n /"variable number tandem repeat"/ (/"VNTR"/) 5' to the MBP gene is the subject of conflicting reports. OBJECTIVE: To study possible MS association with /"VNTR"/ alleles of MBP gene in ethnic Italians and ethnic Russians. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP /"VNTR"/ region and for the human /"leukocyte antigen (HLA) class II DRB1"/ gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the /"DR4"/- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the /"DR4"/- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of /"DR4"/- and DR5-positive Italians and Russians. | [
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12948282 | Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). | OBJECTIVE: Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. METHODS: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. RESULTS: Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). CONCLUSION: These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued. | /"Manganese superoxide dismutase"/ (/"MnSOD"/) polymorphism, alpha-tocopherol supplementation and /"prostate cancer"/ risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). | OBJECTIVE: /"Manganese superoxide dismutase"/ (/"MnSOD"/) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of /"MnSOD"/ in the development of /"prostate cancer"/ in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that /"MnSOD"/ may be associated with /"prostate cancer"/ and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. METHODS: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. RESULTS: Men homozygous for the /"MnSOD"/ ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the /"MnSOD-prostate cancer"/ association. Although there was no difference in the association with disease stage, men homozygous for /"MnSOD"/ ala (compared to /"MnSOD"/ val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). CONCLUSION: These data suggest an effect of the /"MnSOD"/ ala/ala genotype on the development of /"prostate cancer"/. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued. | [
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12948282 | Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). | OBJECTIVE: Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. METHODS: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. RESULTS: Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). CONCLUSION: These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued. | /"Manganese superoxide dismutase"/ (/"MnSOD"/) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene /"cancer"/ prevention study (Finland). | OBJECTIVE: /"Manganese superoxide dismutase"/ (/"MnSOD"/) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of /"MnSOD"/ in the development of prostate cancer in a large, randomized /"cancer"/ prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that /"MnSOD"/ may be associated with prostate cancer and that long-term antioxidant supplementation (alpha-tocopherol 50 mg/day for five to eight years) could modify the effect on risk. METHODS: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. RESULTS: Men homozygous for the /"MnSOD"/ ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha-tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for /"MnSOD"/ ala (compared to /"MnSOD"/ val/val or val/ala) showed a three-fold risk increase for high-grade /"tumors"/ (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). CONCLUSION: These data suggest an effect of the /"MnSOD"/ ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade /"tumors"/ may have prognostic implications that should also be pursued. | [
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12960748 | Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients. | OBJECTIVE: The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity. METHODS: The CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. RESULTS: The allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. CONCLUSION: The present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients. | Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced /"extrapyramidal symptoms"/ in Japanese schizophrenic patients. | OBJECTIVE: The purpose of this study was to examine whether the neuroleptic-induced /"extrapyramidal symptoms"/ are associated with the /"CYP2D6"/ activity. METHODS: The /"CYP2D6"/ gene polymorphisms (/"CYP2D6"/*2, /"CYP2D6"/*3, /"CYP2D6"/*4, /"CYP2D6"/*10, and /"CYP2D6"/*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to /"extrapyramidal symptoms"/ (/"EPS"/) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. RESULTS: The allele frequency of /"CYP2D6"/*2 was significantly higher, while that of /"CYP2D6"/*10 tended to be higher in the schizophrenic patients susceptible to acute /"EPS"/. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of /"CYP2D6"/*2, while this difference was trend level in those of /"CYP2D6"/*10. However, no significant difference was observed in the distribution of both /"CYP2D6"/*2 (C2938T) and /"CYP2D6"/*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. CONCLUSION: The present results suggest that the homozygotes of /"CYP2D6"/*2 and /"CYP2D6"/*10 appear to be a susceptibility factor for developing acute /"EPS"/ in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients. | [
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12960748 | Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients. | OBJECTIVE: The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity. METHODS: The CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. RESULTS: The allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. CONCLUSION: The present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients. | Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese /"schizophrenic"/ patients. | OBJECTIVE: The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the /"CYP2D6"/ activity. METHODS: The /"CYP2D6"/ gene polymorphisms (/"CYP2D6"/*2, /"CYP2D6"/*3, /"CYP2D6"/*4, /"CYP2D6"/*10, and /"CYP2D6"/*12) were genotyped in 196 normal controls and 320 /"schizophrenic"/ patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. RESULTS: The allele frequency of /"CYP2D6"/*2 was significantly higher, while that of /"CYP2D6"/*10 tended to be higher in the /"schizophrenic"/ patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in /"schizophrenic"/ patients with the mutant-type homozygote of /"CYP2D6"/*2, while this difference was trend level in those of /"CYP2D6"/*10. However, no significant difference was observed in the distribution of both /"CYP2D6"/*2 (C2938T) and /"CYP2D6"/*10 (C188T) polymorphisms between /"schizophrenic"/ patients with or without tardive dyskinesia. CONCLUSION: The present results suggest that the homozygotes of /"CYP2D6"/*2 and /"CYP2D6"/*10 appear to be a susceptibility factor for developing acute EPS in /"schizophrenic"/ patients and for impaired neuroleptic metabolism in Japanese /"schizophrenic"/ patients. | [
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12963757 | Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD. | OBJECTIVE: To study the hypotheses that APOE-epsilon4 allele may interact with blood pressure to affect Alzheimer's disease (AD) occurrence and that antihypertensive therapy could modify such an effect. METHODS: A dementia-free cohort of 966 community-dwelling persons aged 75 years and older in Stockholm, Sweden was followed to detect patients with AD using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) diagnostic criteria. Data were analyzed using Cox proportional hazards models with adjustment for several potential confounders. RESULTS: During a 6-year follow-up period, AD was diagnosed in 204 persons. APOE-epsilon4 allele, high systolic pressure (> or = 140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of AD. APOE-epsilon4 allele combined with low diastolic pressure greatly increased the risk of AD independent of antihypertensive drug use. Antihypertensive therapy significantly reduced the risk of AD regardless of APOE-epsilon4 status and counteracted the combined risk effect of the epsilon4 allele with high systolic pressure on the disease. CONCLUSIONS: Elderly people with genetic susceptibility for Alzheimer's disease may experience a further increased disease risk if they have either high systolic pressure or low diastolic pressure. Antihypertensive therapy decreases the risk of Alzheimer's disease exerted by the APOE-epsilon4 allele. | Combined effects of /"APOE"/ genotype, blood pressure, and antihypertensive drug use on incident /"AD"/. | OBJECTIVE: To study the hypotheses that /"APOE"/-epsilon4 allele may interact with blood pressure to affect /"Alzheimer's disease"/ (/"AD"/) occurrence and that antihypertensive therapy could modify such an effect. METHODS: A dementia-free cohort of 966 community-dwelling persons aged 75 years and older in Stockholm, Sweden was followed to detect patients with /"AD"/ using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) diagnostic criteria. Data were analyzed using Cox proportional hazards models with adjustment for several potential confounders. RESULTS: During a 6-year follow-up period, /"AD"/ was diagnosed in 204 persons. /"APOE"/-epsilon4 allele, high systolic pressure (> or = 140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of /"AD"/. /"APOE"/-epsilon4 allele combined with low diastolic pressure greatly increased the risk of /"AD"/ independent of antihypertensive drug use. Antihypertensive therapy significantly reduced the risk of /"AD"/ regardless of /"APOE"/-epsilon4 status and counteracted the combined risk effect of the epsilon4 allele with high systolic pressure on the disease. CONCLUSIONS: Elderly people with genetic susceptibility for /"Alzheimer's disease"/ may experience a further increased disease risk if they have either high systolic pressure or low diastolic pressure. Antihypertensive therapy decreases the risk of /"Alzheimer's disease"/ exerted by the /"APOE"/-epsilon4 allele. | [
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} | Yes |
12963757 | Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD. | OBJECTIVE: To study the hypotheses that APOE-epsilon4 allele may interact with blood pressure to affect Alzheimer's disease (AD) occurrence and that antihypertensive therapy could modify such an effect. METHODS: A dementia-free cohort of 966 community-dwelling persons aged 75 years and older in Stockholm, Sweden was followed to detect patients with AD using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) diagnostic criteria. Data were analyzed using Cox proportional hazards models with adjustment for several potential confounders. RESULTS: During a 6-year follow-up period, AD was diagnosed in 204 persons. APOE-epsilon4 allele, high systolic pressure (> or = 140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of AD. APOE-epsilon4 allele combined with low diastolic pressure greatly increased the risk of AD independent of antihypertensive drug use. Antihypertensive therapy significantly reduced the risk of AD regardless of APOE-epsilon4 status and counteracted the combined risk effect of the epsilon4 allele with high systolic pressure on the disease. CONCLUSIONS: Elderly people with genetic susceptibility for Alzheimer's disease may experience a further increased disease risk if they have either high systolic pressure or low diastolic pressure. Antihypertensive therapy decreases the risk of Alzheimer's disease exerted by the APOE-epsilon4 allele. | Combined effects of /"APOE"/ genotype, blood pressure, and antihypertensive drug use on incident AD. | OBJECTIVE: To study the hypotheses that /"APOE"/-epsilon4 allele may interact with blood pressure to affect Alzheimer's disease (AD) occurrence and that antihypertensive therapy could modify such an effect. METHODS: A /"dementia"/-free cohort of 966 community-dwelling persons aged 75 years and older in Stockholm, Sweden was followed to detect patients with AD using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) diagnostic criteria. Data were analyzed using Cox proportional hazards models with adjustment for several potential confounders. RESULTS: During a 6-year follow-up period, AD was diagnosed in 204 persons. /"APOE"/-epsilon4 allele, high systolic pressure (> or = 140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of AD. /"APOE"/-epsilon4 allele combined with low diastolic pressure greatly increased the risk of AD independent of antihypertensive drug use. Antihypertensive therapy significantly reduced the risk of AD regardless of /"APOE"/-epsilon4 status and counteracted the combined risk effect of the epsilon4 allele with high systolic pressure on the disease. CONCLUSIONS: Elderly people with genetic susceptibility for Alzheimer's disease may experience a further increased disease risk if they have either high systolic pressure or low diastolic pressure. Antihypertensive therapy decreases the risk of Alzheimer's disease exerted by the /"APOE"/-epsilon4 allele. | [
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"entity_id": "D003704",
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"text_name": "dementia"
} | No |
1301936 | A 15-bp deletion in exon 5 of the ornithine aminotransferase (OAT) locus associated with gyrate atrophy. | Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive disorder in which a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) leads to progressive blindness. Previously, we and others have reported a number of missense mutations and splice defects in the OAT gene associated with GA. In the present case, through sequencing of the PCR amplified cDNA products, we have detected a novel 15-bp deletion within exon 5 of the OAT gene which retains the original reading frame. The deleted PCR product is the only one produced from the patient's mRNA, while mRNA from the patient's mother yields both deleted and normal length PCR products. The alternate, apparently nonexpressing OAT allele in this patient was inherited from the father, who displays only the normal length PCR product. The codon at the deletion joint remains unaltered, predicting the loss of the pentapeptide Tyr-Thr-Val-Lys-Gly without any other amino acid change. The breakpoints are adjacent to or within two copies of a 4-bp direct repeat, which may have implications for the mechanism of deletion. | A 15-bp deletion in exon 5 of the /"ornithine aminotransferase"/se"/ (/"OAT"/AT"/) locus associated with gyrate atrophy. | /"Gyrate atrophy of the choroid and retina"/ (GA) is an autosomal recessive disorder in which a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (/"OAT"/) leads to progressive blindness. Previously, we and others have reported a number of missense mutations and splice defects in the /"OAT"/AT"/ gene associated with GA. In the present case, through sequencing of the PCR amplified cDNA products, we have detected a novel 15-bp deletion within exon 5 of the /"OAT"/AT"/ gene which retains the original reading frame. The deleted PCR product is the only one produced from the patient's mRNA, while mRNA from the patient's mother yields both deleted and normal length PCR products. The alternate, apparently nonexpressing /"OAT"/AT"/ allele in this patient was inherited from the father, who displays only the normal length PCR product. The codon at the deletion joint remains unaltered, predicting the loss of the pentapeptide Tyr-Thr-Val-Lys-Gly without any other amino acid change. The breakpoints are adjacent to or within two copies of a 4-bp direct repeat, which may have implications for the mechanism of deletion. | [
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} | {
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"text_name": "Gyrate atrophy of the choroid and retina"
} | Yes |
1301936 | A 15-bp deletion in exon 5 of the ornithine aminotransferase (OAT) locus associated with gyrate atrophy. | Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive disorder in which a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) leads to progressive blindness. Previously, we and others have reported a number of missense mutations and splice defects in the OAT gene associated with GA. In the present case, through sequencing of the PCR amplified cDNA products, we have detected a novel 15-bp deletion within exon 5 of the OAT gene which retains the original reading frame. The deleted PCR product is the only one produced from the patient's mRNA, while mRNA from the patient's mother yields both deleted and normal length PCR products. The alternate, apparently nonexpressing OAT allele in this patient was inherited from the father, who displays only the normal length PCR product. The codon at the deletion joint remains unaltered, predicting the loss of the pentapeptide Tyr-Thr-Val-Lys-Gly without any other amino acid change. The breakpoints are adjacent to or within two copies of a 4-bp direct repeat, which may have implications for the mechanism of deletion. | A 15-bp deletion in exon 5 of the /"ornithine aminotransferase"/ (/"OAT"/) locus associated with gyrate /"atrophy"/. | Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive disorder in which a deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (/"OAT"/) leads to progressive blindness. Previously, we and others have reported a number of missense mutations and splice defects in the /"OAT"/ gene associated with GA. In the present case, through sequencing of the PCR amplified cDNA products, we have detected a novel 15-bp deletion within exon 5 of the /"OAT"/ gene which retains the original reading frame. The deleted PCR product is the only one produced from the patient's mRNA, while mRNA from the patient's mother yields both deleted and normal length PCR products. The alternate, apparently nonexpressing /"OAT"/ allele in this patient was inherited from the father, who displays only the normal length PCR product. The codon at the deletion joint remains unaltered, predicting the loss of the pentapeptide Tyr-Thr-Val-Lys-Gly without any other amino acid change. The breakpoints are adjacent to or within two copies of a 4-bp direct repeat, which may have implications for the mechanism of deletion. | [
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},
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] | {
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"text_name": "OAT"
} | {
"begin_idx": "96",
"end_idx": "103",
"entity_id": "D001284",
"entity_type": "Disease",
"text_name": "atrophy"
} | No |
1352745 | Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon? | Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon. | Normal C3b receptor (/"CR1"/) genomic polymorphism in patients with /"insulin-dependent diabetes mellitus"/ (/"IDDM"/): is the low erythrocyte /"CR1"/ expression an acquired phenomenon? | Expression of the erythrocyte complement receptor (/"C3bR"/ = /"CR1"/ = /"CD35"/) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with /"IDDM"/, 31 healthy siblings and 101 healthy blood donors. Defective /"CR1"/ expression was found in 26% of the patients with /"IDDM"/ compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The /"CR1"/ gene polymorphism of the /"IDDM"/ patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) /"CR1"/ gene fragment was associated with a low /"CR1"/ expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for /"IDDM"/ and /"CR1"/ expression. The results confirm that erythrocyte /"CR1"/ expression is genetically determined, but the /"CR1"/ deficiency associated with /"IDDM"/ seems to be an acquired rather than a genetic phenomenon. | [
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} | Yes |
1363805 | Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. | Medium chain acyl-CoA dehydrogenase (MCAD) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature MCAD subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the MCAD gene and the evolution of 985A-->G mutation are briefly discussed. | Mutations in the /"medium chain acyl-CoA dehydrogenase"/ (/"MCAD"/AD"/) gene. | /"Medium chain acyl-CoA dehydrogenase"/se"/ (/"MCAD"/AD"/) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. /"MCAD deficiency"/ is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature /"MCAD"/AD"/ subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the /"MCAD"/AD"/ gene and the evolution of 985A-->G mutation are briefly discussed. | [
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},
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"text_name": "impairment of tetramer assembly"
},
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} | Yes |
1363805 | Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. | Medium chain acyl-CoA dehydrogenase (MCAD) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature MCAD subunit, which causes impairment of tetramer assembly and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the MCAD gene and the evolution of 985A-->G mutation are briefly discussed. | Mutations in the /"medium chain acyl-CoA dehydrogenase"/ (/"MCAD"/) gene. | /"Medium chain acyl-CoA dehydrogenase"/ (/"MCAD"/) catalyzes the first reaction of the beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the most frequent inborn metabolic disorders in populations of northwestern European origin. In the compilation of data from a worldwide study of 172 unrelated patients each representing an independent pedigree, a total of 8 different mutations have been identified. Among them, a single prevalent mutation, 985A-->G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate substitution for lysine-304 in the mature /"MCAD"/ subunit, which causes /"impairment of tetramer assembly"/ and instability of the protein. Three of 7 rarer mutations have been identified in a few unrelated patients, while the remaining 4 have each been found in only a single pedigree. In addition to tabulating the mutations, the acyl-CoA dehydrogenase gene family, the structure of the /"MCAD"/ gene and the evolution of 985A-->G mutation are briefly discussed. | [
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"text_name": "impairment of tetramer assembly"
} | No |
14502680 | Frequencies of single nucleotide polymorphism in alcohol dehydrogenase7 gene in patients with multiple system atrophy and controls. | A polymerase chain reaction and direct sequencing of the ADH7 gene were carried out in 50 controls and 50 patients with probable multiple system atrophy (MSA). Seven SNPs, one insertion, and one mismatch were found in patients with MSA and controls. There was no significant difference in the frequencies of each SNP between the patients and the controls (P > 0.05). Interpretation of this negative finding should be cautious in view of the relatively small number of cases. | Frequencies of single nucleotide polymorphism in alcohol dehydrogenase7 gene in patients with /"multiple system atrophy"/ and controls. | A polymerase chain reaction and direct sequencing of the /"ADH7"/ gene were carried out in 50 controls and 50 patients with probable /"multiple system atrophy"/ (/"MSA"/). Seven SNPs, one insertion, and one mismatch were found in patients with /"MSA"/ and controls. There was no significant difference in the frequencies of each SNP between the patients and the controls (P > 0.05). Interpretation of this negative finding should be cautious in view of the relatively small number of cases. | [
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} | {
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"entity_id": "D019578",
"entity_type": "Disease",
"text_name": "multiple system atrophy"
} | Yes |
14508190 | An association study of angiotensinogen polymorphisms with serum level and hypertension in an African-American population. | OBJECTIVE: To evaluate the association of angiotensinogen (AGT) gene with AGT level and hypertension based on the overall genetic variation of the AGT gene in among African-Americans. METHODS: All non-rare single nucleotide polymorphisms (SNPs) in AGT were identified by resequencing 24 individuals. Five tagging SNPs were selected based on the pairwised linkage disequilibrium (LD) pattern and were genotyped in 284 individuals. Association studies of AGT level and hypertension were performed using these five tagging SNPs. RESULTS: No significant association with AGT level or hypertension was found in analyses of each of the five single SNPs. However, one of the haplotypes defined by these five SNPs was significantly associated with AGT level (P = 0.046), although this haplotype was not associated with hypertension. CONCLUSIONS: Identification of genetic polymorphisms associated with risk of hypertension has been frustratingly difficult. Two strategies adopted to improve precision are the use of intermediate phenotypes and summarization of genetic information using haplotypes. These strategies appeared to yield a modest increase in precision at the AGT locus with respect to the physiological intermediate, but did not lead to significant association of the molecular markers with hypertension. Additional research is required to increase confidence in haplotype mapping as an epidemiological analysis tool. | An association study of /"angiotensinogen"/ polymorphisms with serum level and /"hypertension"/ in an African-American population. | OBJECTIVE: To evaluate the association of /"angiotensinogen"/ (/"AGT"/) gene with /"AGT"/ level and /"hypertension"/ based on the overall genetic variation of the /"AGT"/ gene in among African-Americans. METHODS: All non-rare single nucleotide polymorphisms (SNPs) in /"AGT"/ were identified by resequencing 24 individuals. Five tagging SNPs were selected based on the pairwised linkage disequilibrium (LD) pattern and were genotyped in 284 individuals. Association studies of /"AGT"/ level and /"hypertension"/ were performed using these five tagging SNPs. RESULTS: No significant association with /"AGT"/ level or /"hypertension"/ was found in analyses of each of the five single SNPs. However, one of the haplotypes defined by these five SNPs was significantly associated with /"AGT"/ level (P = 0.046), although this haplotype was not associated with /"hypertension"/. CONCLUSIONS: Identification of genetic polymorphisms associated with risk of /"hypertension"/ has been frustratingly difficult. Two strategies adopted to improve precision are the use of intermediate phenotypes and summarization of genetic information using haplotypes. These strategies appeared to yield a modest increase in precision at the /"AGT"/ locus with respect to the physiological intermediate, but did not lead to significant association of the molecular markers with /"hypertension"/. Additional research is required to increase confidence in haplotype mapping as an epidemiological analysis tool. | [
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"text_name": "hypertension"
} | Yes |
14521605 | Identification of a novel point mutation in platelet glycoprotein Ibalpha, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. | BACKGROUND: Interaction between platelet glycoprotein (GP)Ibalpha and von Willebrand factor (VWF) has critical roles in both physiological hemostasis and thrombosis. Platelet-type von Willebrand disease (plt-VWD) is a congenital bleeding disorder characterized by gain-of-function mutations of GPIbalpha. To date, two mutations in GPIbalpha, G233V and M239V, have been reported in four unrelated families with plt-VWD. OBJECTIVE: The present study aimed to determine whether G233S of GPIbalpha, a new mutation observed in plt-VWD patients, causes the plt-VWD phenotype and to examine whether conversions to other residues at this position affect VWF binding. PATIENTS AND METHODS: The propositus was a 3-year-old Japanese male. He displayed bleeding symptoms and moderate thrombocytopenia. His brother was similarly affected. Platelets from both patients were analyzed by ristocetin- or shear-induced platelet aggregation. DNA sequencing was performed to analyze the GPIbalpha sequence. We examined the 125I-labeled VWF binding using a series of recombinant GPIbalpha fragments with different residues at position 233 (G233S, G233A, G233K, and G233D) together with naturally occurring mutations previously reported in patients (G233V and M239V). RESULTS: Platelet function analysis indicated that platelets from both patients had a typical plt-VWD phenotype. DNA sequencing analysis showed a heterozygous mutation of Gly to Ser at residue 233 of GPIbalpha in both patients. The 125I-labeled VWF binding to mutant compared with the wild type displayed three patterns, gain-of-function (G233S, G233V, and M239V), equivalent function (G233A), and loss-of-function (G233K and G233D). CONCLUSIONS: The G233S is a molecular basis of plt-VWD, and residue 233 plays critical roles in regulating VWF binding. | Identification of a novel point mutation in platelet /"glycoprotein Ibalpha"/, Gly to Ser at residue 233, in a Japanese family with /"platelet-type von Willebrand disease"/. | BACKGROUND: Interaction between platelet glycoprotein (GP)Ibalpha and von Willebrand factor (VWF) has critical roles in both physiological hemostasis and thrombosis. /"Platelet-type von Willebrand disease"/ (/"plt-VWD"/) is a congenital bleeding disorder characterized by gain-of-function mutations of /"GPIbalpha"/. To date, two mutations in /"GPIbalpha"/, G233V and M239V, have been reported in four unrelated families with /"plt-VWD"/. OBJECTIVE: The present study aimed to determine whether G233S of /"GPIbalpha"/, a new mutation observed in /"plt-VWD"/ patients, causes the /"plt-VWD"/ phenotype and to examine whether conversions to other residues at this position affect VWF binding. PATIENTS AND METHODS: The propositus was a 3-year-old Japanese male. He displayed bleeding symptoms and moderate thrombocytopenia. His brother was similarly affected. Platelets from both patients were analyzed by ristocetin- or shear-induced platelet aggregation. DNA sequencing was performed to analyze the /"GPIbalpha"/ sequence. We examined the 125I-labeled VWF binding using a series of recombinant /"GPIbalpha"/ fragments with different residues at position 233 (G233S, G233A, G233K, and G233D) together with naturally occurring mutations previously reported in patients (G233V and M239V). RESULTS: Platelet function analysis indicated that platelets from both patients had a typical /"plt-VWD"/ phenotype. DNA sequencing analysis showed a heterozygous mutation of Gly to Ser at residue 233 of /"GPIbalpha"/ in both patients. The 125I-labeled VWF binding to mutant compared with the wild type displayed three patterns, gain-of-function (G233S, G233V, and M239V), equivalent function (G233A), and loss-of-function (G233K and G233D). CONCLUSIONS: The G233S is a molecular basis of /"plt-VWD"/, and residue 233 plays critical roles in regulating VWF binding. | [
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},
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},
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},
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"text_name": "thrombosis"
},
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},
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},
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},
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},
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},
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},
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},
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"text_name": "VWF"
},
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},
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] | {
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} | {
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"entity_id": "C536458",
"entity_type": "Disease",
"text_name": "platelet-type von Willebrand disease"
} | Yes |
14521605 | Identification of a novel point mutation in platelet glycoprotein Ibalpha, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. | BACKGROUND: Interaction between platelet glycoprotein (GP)Ibalpha and von Willebrand factor (VWF) has critical roles in both physiological hemostasis and thrombosis. Platelet-type von Willebrand disease (plt-VWD) is a congenital bleeding disorder characterized by gain-of-function mutations of GPIbalpha. To date, two mutations in GPIbalpha, G233V and M239V, have been reported in four unrelated families with plt-VWD. OBJECTIVE: The present study aimed to determine whether G233S of GPIbalpha, a new mutation observed in plt-VWD patients, causes the plt-VWD phenotype and to examine whether conversions to other residues at this position affect VWF binding. PATIENTS AND METHODS: The propositus was a 3-year-old Japanese male. He displayed bleeding symptoms and moderate thrombocytopenia. His brother was similarly affected. Platelets from both patients were analyzed by ristocetin- or shear-induced platelet aggregation. DNA sequencing was performed to analyze the GPIbalpha sequence. We examined the 125I-labeled VWF binding using a series of recombinant GPIbalpha fragments with different residues at position 233 (G233S, G233A, G233K, and G233D) together with naturally occurring mutations previously reported in patients (G233V and M239V). RESULTS: Platelet function analysis indicated that platelets from both patients had a typical plt-VWD phenotype. DNA sequencing analysis showed a heterozygous mutation of Gly to Ser at residue 233 of GPIbalpha in both patients. The 125I-labeled VWF binding to mutant compared with the wild type displayed three patterns, gain-of-function (G233S, G233V, and M239V), equivalent function (G233A), and loss-of-function (G233K and G233D). CONCLUSIONS: The G233S is a molecular basis of plt-VWD, and residue 233 plays critical roles in regulating VWF binding. | Identification of a novel point mutation in platelet /"glycoprotein Ibalpha"/, Gly to Ser at residue 233, in a Japanese family with platelet-type von Willebrand disease. | BACKGROUND: Interaction between platelet glycoprotein (GP)Ibalpha and von Willebrand factor (VWF) has critical roles in both physiological hemostasis and thrombosis. Platelet-type von Willebrand disease (plt-VWD) is a congenital bleeding disorder characterized by gain-of-function mutations of /"GPIbalpha"/. To date, two mutations in /"GPIbalpha"/, G233V and M239V, have been reported in four unrelated families with plt-VWD. OBJECTIVE: The present study aimed to determine whether G233S of /"GPIbalpha"/, a new mutation observed in plt-VWD patients, causes the plt-VWD phenotype and to examine whether conversions to other residues at this position affect VWF binding. PATIENTS AND METHODS: The propositus was a 3-year-old Japanese male. He displayed /"bleeding"/ symptoms and moderate thrombocytopenia. His brother was similarly affected. Platelets from both patients were analyzed by ristocetin- or shear-induced platelet aggregation. DNA sequencing was performed to analyze the /"GPIbalpha"/ sequence. We examined the 125I-labeled VWF binding using a series of recombinant /"GPIbalpha"/ fragments with different residues at position 233 (G233S, G233A, G233K, and G233D) together with naturally occurring mutations previously reported in patients (G233V and M239V). RESULTS: Platelet function analysis indicated that platelets from both patients had a typical plt-VWD phenotype. DNA sequencing analysis showed a heterozygous mutation of Gly to Ser at residue 233 of /"GPIbalpha"/ in both patients. The 125I-labeled VWF binding to mutant compared with the wild type displayed three patterns, gain-of-function (G233S, G233V, and M239V), equivalent function (G233A), and loss-of-function (G233K and G233D). CONCLUSIONS: The G233S is a molecular basis of plt-VWD, and residue 233 plays critical roles in regulating VWF binding. | [
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14558082 | Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | Polymorphisms in the /"interferon-gamma"//interleukin-26 gene region contribute to sex bias in susceptibility to /"rheumatoid arthritis"/. | OBJECTIVE: To determine whether polymorphisms in the /"interferon-gamma"/ (/"IFNgamma"/)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to /"rheumatoid arthritis"/ (/"RA"/). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the /"IFNgamma"/ and IL-26 genes on chromosome 12q15, were typed in 251 patients with /"RA"/ and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with /"RA"/ in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with /"RA"/ (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with /"RA"/. CONCLUSION: Our results demonstrate that common polymorphisms in the /"IFNgamma"//IL-26 gene region may contribute to sex bias in susceptibility to /"RA"/, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | [
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} | Yes |
14558082 | Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | Polymorphisms in the interferon-gamma//"interleukin-26"/ gene region contribute to sex bias in susceptibility to /"rheumatoid arthritis"/. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)//"interleukin-26"/ (/"IL-26"/; formerly, /"AK155"/) gene cluster contribute to sex-based differential susceptibility to /"rheumatoid arthritis"/ (/"RA"/). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and /"IL-26"/ genes on chromosome 12q15, were typed in 251 patients with /"RA"/ and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the /"IL-26"/ gene, was significantly associated with /"RA"/ in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with /"RA"/ (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with /"RA"/. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma//"IL-26"/ gene region may contribute to sex bias in susceptibility to /"RA"/, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | [
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} | Yes |
14558082 | Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | Polymorphisms in the /"interferon-gamma"//interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the /"interferon-gamma"/ (/"IFNgamma"/)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the /"IFNgamma"/ and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the /"IFNgamma"//IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, /"multiple sclerosis"/. | [
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"text_name": "multiple sclerosis"
} | No |
14558082 | Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis. | Polymorphisms in the interferon-gamma//"interleukin-26"/ gene region contribute to sex bias in susceptibility to rheumatoid arthritis. | OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)//"interleukin-26"/ (/"IL-26"/; formerly, /"AK155"/) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and /"IL-26"/ genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the /"IL-26"/ gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma//"IL-26"/ gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, /"multiple sclerosis"/. | [
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14563640 | Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. | We report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants. | Molecular characterization of /"ADAMTS13"/ gene mutations in Japanese patients with /"Upshaw-Schulman syndrome"/. | We report here 7 new mutations in the /"ADAMTS13"/ gene responsible for /"Upshaw-Schulman syndrome"/ (/"USS"/), a catastrophic phenotype of /"congenital thrombotic thrombocytopenic purpura"/, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of /"ADAMTS13"/. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with /"USS"/ with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on /"ADAMTS13"/ gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of /"ADAMTS13"/ suggest that the missense mutations could cause structural defects in the mutants. | [
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14563640 | Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. | We report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants. | Molecular characterization of /"ADAMTS13"/ gene mutations in Japanese patients with Upshaw-Schulman syndrome. | We report here 7 new mutations in the /"ADAMTS13"/ gene responsible for Upshaw-Schulman syndrome (USS), a /"catastrophic"/ phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of /"ADAMTS13"/. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on /"ADAMTS13"/ gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of /"ADAMTS13"/ suggest that the missense mutations could cause structural defects in the mutants. | [
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14567462 | Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. | AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | Novel association of HLA-haplotypes with /"primary sclerosing cholangitis"/ (/"PSC"/) in a southern European population. | AIMS: In patients with with /"primary sclerosing cholangitis"/ we investigated the major histocompatibility complex (MHC) genes and mutations of the /"cystic fibrosis transmembrane conductance regulator"/ (/"CFTR"/) gene. METHODS: In 64 /"PSC"/ patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in /"CFTR"/ gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in /"PSC"/ patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in /"PSC"/ patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the /"CFTR"/ gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | [
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} | Yes |
14567462 | Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. | AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | Novel association of HLA-haplotypes with /"primary sclerosing cholangitis"/ (/"PSC"/) in a southern European population. | AIMS: In patients with with /"primary sclerosing cholangitis"/ we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 /"PSC"/ patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, /"HLA-DQB1"/ and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, /"DQB1"/*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, /"DQB1"/*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, /"DQB1"/*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in /"PSC"/ patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, /"DQB1"/*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, /"DQB1"/*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in /"PSC"/ patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | [
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} | Yes |
14567462 | Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. | AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | Novel association of HLA-haplotypes with /"primary sclerosing cholangitis"/ (/"PSC"/) in a southern European population. | AIMS: In patients with with /"primary sclerosing cholangitis"/ we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 /"PSC"/ patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: /"HLA-DRB1"/, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of /"DRB1"/*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), /"DRB1"/*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and /"DRB1"/*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in /"PSC"/ patients. The frequency of patients positive for /"HLA DRB1"/*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). /"DRB1"/*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing /"HLA-DRB1"/*01, *1601, *04 related haplotype sharing patients, /"HLA-DRB1"/*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in /"PSC"/ patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | [
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},
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}
] | {
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} | Yes |
14567462 | Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. | AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | Novel association of HLA-haplotypes with /"primary sclerosing cholangitis"/ (/"PSC"/) in a southern European population. | AIMS: In patients with with /"primary sclerosing cholangitis"/ we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 /"PSC"/ patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, /"tumour necrosis factor A"/ (/"TNFA"/), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in /"PSC"/ patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in /"PSC"/ patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | [
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14567462 | Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in a southern European population. | AIMS: In patients with with primary sclerosing cholangitis we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in PSC patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | Novel association of HLA-haplotypes with /"primary sclerosing cholangitis"/ (/"PSC"/) in a southern European population. | AIMS: In patients with with /"primary sclerosing cholangitis"/ we investigated the major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. METHODS: In 64 /"PSC"/ patients and 183 normal controls of the same population (Northern Italy), allelic polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1, HLA-DQB1 and /"HLA-B"/, tumour necrosis factor A (TNFA), and in CFTR gene, with polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01, DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs. 3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were more elevated in /"PSC"/ patients. The frequency of patients positive for HLA DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%, p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was significantly increased in /"PSC"/ patients (23 vs. 14%, p<0.025), as well as the TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not increased. CONCLUSION: These data suggest that the role of genes in the HLA region is relevant, but not necessarily disease-specific and it might be different in populations with divergent ancestries. | [
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