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19066720 | Candidate genes for temporal lobe epilepsy: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in temporal lobe epilepsy (TLE): interleukin 1beta (IL-1beta), interleukin 1beta (IL-1alpha), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated TLE patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and IL-1RA genes in TLE disease, but failed to confirm the involvement of IL-1beta and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | Candidate genes for /"temporal lobe epilepsy"/: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in /"temporal lobe epilepsy"/ (/"TLE"/): interleukin 1beta (IL-1beta), interleukin 1beta (IL-1alpha), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (/"PDYN"/). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated /"TLE"/ patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and IL-1RA genes in /"TLE disease"/, but failed to confirm the involvement of IL-1beta and /"PDYN"/. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | [
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19066720 | Candidate genes for temporal lobe epilepsy: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in temporal lobe epilepsy (TLE): interleukin 1beta (IL-1beta), interleukin 1beta (IL-1alpha), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated TLE patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and IL-1RA genes in TLE disease, but failed to confirm the involvement of IL-1beta and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | Candidate genes for /"temporal lobe epilepsy"/: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in /"temporal lobe epilepsy"/ (/"TLE"/): /"interleukin 1beta"/ (/"IL-1beta"/), /"interleukin 1beta"/ (IL-1alpha), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated /"TLE"/ patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and IL-1RA genes in /"TLE disease"/, but failed to confirm the involvement of /"IL-1beta"/ and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | [
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19066720 | Candidate genes for temporal lobe epilepsy: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in temporal lobe epilepsy (TLE): interleukin 1beta (IL-1beta), interleukin 1beta (IL-1alpha), interleukin 1RA (IL-1RA), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated TLE patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and IL-1RA genes in TLE disease, but failed to confirm the involvement of IL-1beta and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | Candidate genes for /"temporal lobe epilepsy"/: a replication study. | The objective of this study is to replicate previously published results regarding the involvement of several susceptibility genes in /"temporal lobe epilepsy"/ (/"TLE"/): interleukin 1beta (IL-1beta), interleukin 1beta (IL-1alpha), /"interleukin 1RA"/ (/"IL-1RA"/), apolipoprotein E (ApoE) and prodynorphin (PDYN). We used a case-control approach comparing several polymorphisms within these candidate genes between unrelated /"TLE"/ patients and matched controls. We were thus able to confirm the role of ApoE, IL-1alpha and /"IL-1RA"/ genes in /"TLE disease"/, but failed to confirm the involvement of IL-1beta and PDYN. This failure should be interpreted with caution, as this may be due to the small size of our study groups and the resultant lack of statistical power. | [
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19070929 | A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. METHODS: The CHI3L1 -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: CHI3L1 -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P=0.002). CONCLUSIONS: The CHI3L1 promoter polymorphism -131G-->C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. | A functional variation in /"CHI3L1"/ is associated with severity of /"liver fibrosis"/ and /"YKL-40"/ serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: /"YKL-40"/ is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in /"CHI3L1"/, encoding /"YKL-40"/, is associated with HCV-induced /"liver fibrosis"/ and influences /"YKL-40"/ serum concentrations. METHODS: The /"CHI3L1"/ -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and /"YKL-40"/ serum levels (ELISA) were associated with /"CHI3L1"/ -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: /"CHI3L1"/ -131G-->C genotype was strongly associated with the stage of /"liver fibrosis"/ in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of /"YKL-40"/ in HCV infected patients (P=0.002). CONCLUSIONS: The /"CHI3L1"/ promoter polymorphism -131G-->C determines /"YKL-40"/ serum levels and is associated with the severity of HCV-induced /"liver fibrosis"/. These results suggest a functional role of /"YKL-40"/ in liver fibrogenesis and should be taken into account when using /"YKL-40"/ as a non-invasive fibrosis marker. | [
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19070929 | A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. METHODS: The CHI3L1 -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: CHI3L1 -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P=0.002). CONCLUSIONS: The CHI3L1 promoter polymorphism -131G-->C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. | A functional variation in /"CHI3L1"/ is associated with severity of liver fibrosis and /"YKL-40"/ serum levels in /"chronic hepatitis C infection"/. | BACKGROUND/AIMS: /"YKL-40"/ is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in /"CHI3L1"/, encoding /"YKL-40"/, is associated with HCV-induced liver fibrosis and influences /"YKL-40"/ serum concentrations. METHODS: The /"CHI3L1"/ -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and /"YKL-40"/ serum levels (ELISA) were associated with /"CHI3L1"/ -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: /"CHI3L1"/ -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of /"YKL-40"/ in HCV infected patients (P=0.002). CONCLUSIONS: The /"CHI3L1"/ promoter polymorphism -131G-->C determines /"YKL-40"/ serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of /"YKL-40"/ in liver fibrogenesis and should be taken into account when using /"YKL-40"/ as a non-invasive fibrosis marker. | [
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19070929 | A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. METHODS: The CHI3L1 -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: CHI3L1 -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P=0.002). CONCLUSIONS: The CHI3L1 promoter polymorphism -131G-->C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. | A functional variation in /"CHI3L1"/ is associated with severity of liver fibrosis and /"YKL-40"/ serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: /"YKL-40"/ is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in /"CHI3L1"/, encoding /"YKL-40"/, is associated with HCV-induced liver fibrosis and influences /"YKL-40"/ serum concentrations. METHODS: The /"CHI3L1"/ -131G-->C promoter polymorphism was genotyped in two cohorts of /"HCV infected"/ patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and /"YKL-40"/ serum levels (ELISA) were associated with /"CHI3L1"/ -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: /"CHI3L1"/ -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of /"YKL-40"/ in /"HCV infected"/ patients (P=0.002). CONCLUSIONS: The /"CHI3L1"/ promoter polymorphism -131G-->C determines /"YKL-40"/ serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of /"YKL-40"/ in liver fibrogenesis and should be taken into account when using /"YKL-40"/ as a non-invasive fibrosis marker. | [
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19070929 | A functional variation in CHI3L1 is associated with severity of liver fibrosis and YKL-40 serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. METHODS: The CHI3L1 -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: CHI3L1 -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P=0.002). CONCLUSIONS: The CHI3L1 promoter polymorphism -131G-->C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. | A functional variation in /"CHI3L1"/ is associated with severity of liver fibrosis and /"YKL-40"/ serum levels in chronic hepatitis C infection. | BACKGROUND/AIMS: /"YKL-40"/ is a chitinase-like protein involved in matrix remodelling and a non-invasive /"fibrosis"/ marker. We assessed whether a functional promoter polymorphism in /"CHI3L1"/, encoding /"YKL-40"/, is associated with HCV-induced liver fibrosis and influences /"YKL-40"/ serum concentrations. METHODS: The /"CHI3L1"/ -131G-->C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n=440) by 5'-endonuclease assays. Histological /"fibrosis"/ scores and /"YKL-40"/ serum levels (ELISA) were associated with /"CHI3L1"/ -131G-->C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. RESULTS: /"CHI3L1"/ -131G-->C genotype was strongly associated with the stage of liver fibrosis in the screening (n=265, P=0.001) and validation cohort (n=175, P=0.009). Homozygous carriers of the G allele were protected from severe /"fibrosis"/ (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of /"YKL-40"/ in HCV infected patients (P=0.002). CONCLUSIONS: The /"CHI3L1"/ promoter polymorphism -131G-->C determines /"YKL-40"/ serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of /"YKL-40"/ in liver fibrogenesis and should be taken into account when using /"YKL-40"/ as a non-invasive /"fibrosis"/ marker. | [
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19073975 | An obesity-associated FTO gene variant and increased energy intake in children. | BACKGROUND: Variation in the fat mass and obesity-associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown. METHODS: We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for FTO variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the FTO variant with adiposity, energy expenditure, and food intake. RESULTS: In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to obesity in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82). CONCLUSIONS: The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. | An /"obesity"/-associated /"FTO"/ gene variant and increased energy intake in children. | BACKGROUND: Variation in the fat mass and /"obesity"/-associated (/"FTO"/) gene has provided the most robust associations with common /"obesity"/ to date. However, the role of /"FTO"/ variants in modulating specific components of energy balance is unknown. METHODS: We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for /"FTO"/ variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the /"FTO"/ variant with adiposity, energy expenditure, and food intake. RESULTS: In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to /"obesity"/ in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82). CONCLUSIONS: The /"FTO"/ variant that confers a predisposition to /"obesity"/ does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods. | [
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19079260 | Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity. | Genome-wide association yields new sequence variants at seven loci that associate with measures of /"obesity"/. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of /"obesity"/, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on /"obesity"/-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, /"MC4R"/, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with /"obesity"/. | [
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19079260 | Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity. | Genome-wide association yields new sequence variants at seven loci that associate with measures of /"obesity"/. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of /"obesity"/, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on /"obesity"/-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the /"FTO"/, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with /"obesity"/. | [
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19079260 | Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity. | Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the /"Diabetes Genetics Initiative"/ (/"DGI"/) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and /"SH2B1"/ genes, in addition to variants at seven loci not previously connected with obesity. | [
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19079260 | Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity. | Genome-wide association yields new sequence variants at seven loci that associate with measures of /"obesity"/. | Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of /"obesity"/, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on /"obesity"/-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, /"BDNF"/ and SH2B1 genes, in addition to variants at seven loci not previously connected with /"obesity"/. | [
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19080705 | [Association of PAX1 gene polymorphisms with susceptibility to congenital scoliosis in Chinese Han population]. | OBJECTIVE: To investigate the association of polymorphisms of PAX1 gene with congenital scoliosis (CS) in Chinese Han population and the relationship between the PAX1 gene polymorphisms and the clinical phenotypes of CS. METHODS: Peripheral blood samples were collected from 127 CS patients, 55 male and 72 female, aged (12.9 +/- 4.3) (2 - 23), and 127 sex- and age-matched controls. Based on genotype data from the International HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected using Haploview 4.0 software. Hardy-Weinberg equilibrium was analyzed both in the control and case groups. The case group was classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations, and neural canal deformity. Genotyping of all selected SNPs was done by SNPstream technology. The association between phenotypes and SNP was analyzed. Pairwise linkage disequilibrium was calculated in the control population using Haploview 4.0 software. RESULTS: The sites: SNP1 (rs17861031) and SNP2 (rs6047590), of PAX1 gene were genotyped and both polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in these 2 groups. There was no linkage disequilibrium between these 2 SNPs. The genotype frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2AA, SNP2AT, and SNP2TT of the case group were 2%, 26%, 72%, 2%, 19%, and 80% respectively, all not significantly different from those of the control group (2%, 26%, 72%, 2%, 26%, and 82% respectively, all P > 0.05). The allele frequencies of SNP1A, SNP1G, SNP2A, and SNP2T of the case group were 15%, 85%, 11%, and 89% respectively, all not significantly different from those of the control group (15%, 85%, 10%, and 90% respectively, all P > 0.05). No positive sites were found in different clinical phenotypes. CONCLUSION: The genetic variants of PAX1 gene may not be associated with the susceptibility to CS and different clinical phenotypes of CS in Chinese Han population. | [Association of /"PAX1"/ gene polymorphisms with susceptibility to /"congenital scoliosis"/ in Chinese Han population]. | OBJECTIVE: To investigate the association of polymorphisms of /"PAX1"/ gene with /"congenital scoliosis"/ (/"CS"/) in Chinese Han population and the relationship between the /"PAX1"/ gene polymorphisms and the clinical phenotypes of /"CS"/. METHODS: Peripheral blood samples were collected from 127 /"CS"/ patients, 55 male and 72 female, aged (12.9 +/- 4.3) (2 - 23), and 127 sex- and age-matched controls. Based on genotype data from the International HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected using Haploview 4.0 software. Hardy-Weinberg equilibrium was analyzed both in the control and case groups. The case group was classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations, and neural canal deformity. Genotyping of all selected SNPs was done by SNPstream technology. The association between phenotypes and SNP was analyzed. Pairwise linkage disequilibrium was calculated in the control population using Haploview 4.0 software. RESULTS: The sites: SNP1 (rs17861031) and SNP2 (rs6047590), of /"PAX1"/ gene were genotyped and both polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in these 2 groups. There was no linkage disequilibrium between these 2 SNPs. The genotype frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2AA, SNP2AT, and SNP2TT of the case group were 2%, 26%, 72%, 2%, 19%, and 80% respectively, all not significantly different from those of the control group (2%, 26%, 72%, 2%, 26%, and 82% respectively, all P > 0.05). The allele frequencies of SNP1A, SNP1G, SNP2A, and SNP2T of the case group were 15%, 85%, 11%, and 89% respectively, all not significantly different from those of the control group (15%, 85%, 10%, and 90% respectively, all P > 0.05). No positive sites were found in different clinical phenotypes. CONCLUSION: The genetic variants of /"PAX1"/ gene may not be associated with the susceptibility to /"CS"/ and different clinical phenotypes of /"CS"/ in Chinese Han population. | [
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19080705 | [Association of PAX1 gene polymorphisms with susceptibility to congenital scoliosis in Chinese Han population]. | OBJECTIVE: To investigate the association of polymorphisms of PAX1 gene with congenital scoliosis (CS) in Chinese Han population and the relationship between the PAX1 gene polymorphisms and the clinical phenotypes of CS. METHODS: Peripheral blood samples were collected from 127 CS patients, 55 male and 72 female, aged (12.9 +/- 4.3) (2 - 23), and 127 sex- and age-matched controls. Based on genotype data from the International HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected using Haploview 4.0 software. Hardy-Weinberg equilibrium was analyzed both in the control and case groups. The case group was classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations, and neural canal deformity. Genotyping of all selected SNPs was done by SNPstream technology. The association between phenotypes and SNP was analyzed. Pairwise linkage disequilibrium was calculated in the control population using Haploview 4.0 software. RESULTS: The sites: SNP1 (rs17861031) and SNP2 (rs6047590), of PAX1 gene were genotyped and both polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in these 2 groups. There was no linkage disequilibrium between these 2 SNPs. The genotype frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2AA, SNP2AT, and SNP2TT of the case group were 2%, 26%, 72%, 2%, 19%, and 80% respectively, all not significantly different from those of the control group (2%, 26%, 72%, 2%, 26%, and 82% respectively, all P > 0.05). The allele frequencies of SNP1A, SNP1G, SNP2A, and SNP2T of the case group were 15%, 85%, 11%, and 89% respectively, all not significantly different from those of the control group (15%, 85%, 10%, and 90% respectively, all P > 0.05). No positive sites were found in different clinical phenotypes. CONCLUSION: The genetic variants of PAX1 gene may not be associated with the susceptibility to CS and different clinical phenotypes of CS in Chinese Han population. | [Association of PAX1 gene polymorphisms with susceptibility to /"congenital scoliosis"/ in Chinese Han population]. | OBJECTIVE: To investigate the association of polymorphisms of PAX1 gene with /"congenital scoliosis"/ (/"CS"/) in Chinese Han population and the relationship between the PAX1 gene polymorphisms and the clinical phenotypes of /"CS"/. METHODS: Peripheral blood samples were collected from 127 /"CS"/ patients, 55 male and 72 female, aged (12.9 +/- 4.3) (2 - 23), and 127 sex- and age-matched controls. Based on genotype data from the International HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected using Haploview 4.0 software. Hardy-Weinberg equilibrium was analyzed both in the control and case groups. The case group was classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations, and neural canal deformity. Genotyping of all selected SNPs was done by SNPstream technology. The association between phenotypes and SNP was analyzed. Pairwise linkage disequilibrium was calculated in the control population using Haploview 4.0 software. RESULTS: The sites: /"SNP1"/ (rs17861031) and SNP2 (rs6047590), of PAX1 gene were genotyped and both polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in these 2 groups. There was no linkage disequilibrium between these 2 SNPs. The genotype frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2AA, SNP2AT, and SNP2TT of the case group were 2%, 26%, 72%, 2%, 19%, and 80% respectively, all not significantly different from those of the control group (2%, 26%, 72%, 2%, 26%, and 82% respectively, all P > 0.05). The allele frequencies of SNP1A, SNP1G, SNP2A, and SNP2T of the case group were 15%, 85%, 11%, and 89% respectively, all not significantly different from those of the control group (15%, 85%, 10%, and 90% respectively, all P > 0.05). No positive sites were found in different clinical phenotypes. CONCLUSION: The genetic variants of PAX1 gene may not be associated with the susceptibility to /"CS"/ and different clinical phenotypes of /"CS"/ in Chinese Han population. | [
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19094875 | [Effect of polymorphisms of the cathecol-O-methyltransferase on schizophrenia risk in a Spanish population]. | BACKGROUND AND OBJECTIVE: Cathecol-O-methyl transferase (COMT) is one of the most plausible susceptibility genes of schizophrenia risk. The main genetic variant (G158A or rs4680) studied is functional. It has been shown that G-A transition at COMT codon 158 makes COMT more thermolabile and less active at physiological temperature. Genetic variants in the P2 promoter have been suggested to cause alterations in brain COMT protein levels. A variant in the P2 promoter (-278A/G or rs1800706) has recently been associated with psychotic disorders. We studied whether polymorphisms in COMT (G158A, -278A/G) are risk factors for schizophrenia in a Spanish population. PATIENTS AND METHOD: 243 subjects diagnosed of schizophrenia and related disorders following the DSM-IV criteria and 291 hospital-based controls participated in an association study. RESULTS: The heterozygotes for the COMT -278A/G polymorphism showed a 60% reduction in the schizophrenia risk (p = 0.009). No significant differences were observed between the other COMT genotypes or haplotypes in cases and controls. CONCLUSIONS: Our results suggest that the COMT -278A/G polymorphism may have a role in schizophrenia. The results are in agreement with recent findings in this field that indicate a minor influence of COMT G158A on schizophrenia risk and a greater importance of polymorphisms in the P2 promoter regions of COMT, such as -278A/G. | [Effect of polymorphisms of the cathecol-O-methyltransferase on /"schizophrenia"/ risk in a Spanish population]. | BACKGROUND AND OBJECTIVE: /"Cathecol-O-methyl transferase"/ (/"COMT"/) is one of the most plausible susceptibility genes of /"schizophrenia"/ risk. The main genetic variant (G158A or rs4680) studied is functional. It has been shown that G-A transition at /"COMT"/ codon 158 makes /"COMT"/ more thermolabile and less active at physiological temperature. Genetic variants in the P2 promoter have been suggested to cause alterations in brain /"COMT"/ protein levels. A variant in the P2 promoter (-278A/G or rs1800706) has recently been associated with psychotic disorders. We studied whether polymorphisms in /"COMT"/ (G158A, -278A/G) are risk factors for /"schizophrenia"/ in a Spanish population. PATIENTS AND METHOD: 243 subjects diagnosed of /"schizophrenia"/ and related disorders following the DSM-IV criteria and 291 hospital-based controls participated in an association study. RESULTS: The heterozygotes for the /"COMT"/ -278A/G polymorphism showed a 60% reduction in the /"schizophrenia"/ risk (p = 0.009). No significant differences were observed between the other /"COMT"/ genotypes or haplotypes in cases and controls. CONCLUSIONS: Our results suggest that the /"COMT"/ -278A/G polymorphism may have a role in /"schizophrenia"/. The results are in agreement with recent findings in this field that indicate a minor influence of /"COMT"/ G158A on /"schizophrenia"/ risk and a greater importance of polymorphisms in the P2 promoter regions of /"COMT"/, such as -278A/G. | [
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} | {
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"entity_id": "D012559",
"entity_type": "Disease",
"text_name": "schizophrenia"
} | Yes |
19094875 | [Effect of polymorphisms of the cathecol-O-methyltransferase on schizophrenia risk in a Spanish population]. | BACKGROUND AND OBJECTIVE: Cathecol-O-methyl transferase (COMT) is one of the most plausible susceptibility genes of schizophrenia risk. The main genetic variant (G158A or rs4680) studied is functional. It has been shown that G-A transition at COMT codon 158 makes COMT more thermolabile and less active at physiological temperature. Genetic variants in the P2 promoter have been suggested to cause alterations in brain COMT protein levels. A variant in the P2 promoter (-278A/G or rs1800706) has recently been associated with psychotic disorders. We studied whether polymorphisms in COMT (G158A, -278A/G) are risk factors for schizophrenia in a Spanish population. PATIENTS AND METHOD: 243 subjects diagnosed of schizophrenia and related disorders following the DSM-IV criteria and 291 hospital-based controls participated in an association study. RESULTS: The heterozygotes for the COMT -278A/G polymorphism showed a 60% reduction in the schizophrenia risk (p = 0.009). No significant differences were observed between the other COMT genotypes or haplotypes in cases and controls. CONCLUSIONS: Our results suggest that the COMT -278A/G polymorphism may have a role in schizophrenia. The results are in agreement with recent findings in this field that indicate a minor influence of COMT G158A on schizophrenia risk and a greater importance of polymorphisms in the P2 promoter regions of COMT, such as -278A/G. | [Effect of polymorphisms of the cathecol-O-methyltransferase on schizophrenia risk in a Spanish population]. | BACKGROUND AND OBJECTIVE: /"Cathecol-O-methyl transferase"/ (/"COMT"/) is one of the most plausible susceptibility genes of schizophrenia risk. The main genetic variant (G158A or rs4680) studied is functional. It has been shown that G-A transition at /"COMT"/ codon 158 makes /"COMT"/ more thermolabile and less active at physiological temperature. Genetic variants in the P2 promoter have been suggested to cause alterations in brain /"COMT"/ protein levels. A variant in the P2 promoter (-278A/G or rs1800706) has recently been associated with /"psychotic disorders"/. We studied whether polymorphisms in /"COMT"/ (G158A, -278A/G) are risk factors for schizophrenia in a Spanish population. PATIENTS AND METHOD: 243 subjects diagnosed of schizophrenia and related disorders following the DSM-IV criteria and 291 hospital-based controls participated in an association study. RESULTS: The heterozygotes for the /"COMT"/ -278A/G polymorphism showed a 60% reduction in the schizophrenia risk (p = 0.009). No significant differences were observed between the other /"COMT"/ genotypes or haplotypes in cases and controls. CONCLUSIONS: Our results suggest that the /"COMT"/ -278A/G polymorphism may have a role in schizophrenia. The results are in agreement with recent findings in this field that indicate a minor influence of /"COMT"/ G158A on schizophrenia risk and a greater importance of polymorphisms in the P2 promoter regions of /"COMT"/, such as -278A/G. | [
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] | {
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} | {
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} | No |
19104460 | Interaction between PON1 and population density in amyotrophic lateral sclerosis. | Paraoxonase polymorphisms have been associated with amyotrophic lateral sclerosis (ALS). Paraoxonases are detoxifying enzymes involved in the metabolism of organophosphates. We tested the hypothesis that genetic variation within paraoxonase genes would interact with the environmental exposure to paraoxonase substrates. We used population density in the location of residence of ALS patients as a surrogate marker for environmental exposure. Paraoxonase genotypes at previously associated single nucleotide polymorphisms rs662, rs854560, rs6954345, and rs11981433 were studied in 98 patients from the South East England ALS population-based register. A case-only analysis was carried out and median population density was used to categorize patients into rural or urban environments. We found a significant interaction with population density for marker rs854560 (L55M) in ALS. | Interaction between /"PON1"/ and population density in /"amyotrophic lateral sclerosis"/. | Paraoxonase polymorphisms have been associated with /"amyotrophic lateral sclerosis"/ (/"ALS"/). Paraoxonases are detoxifying enzymes involved in the metabolism of organophosphates. We tested the hypothesis that genetic variation within paraoxonase genes would interact with the environmental exposure to paraoxonase substrates. We used population density in the location of residence of /"ALS"/ patients as a surrogate marker for environmental exposure. Paraoxonase genotypes at previously associated single nucleotide polymorphisms rs662, rs854560, rs6954345, and rs11981433 were studied in 98 patients from the South East England /"ALS"/ population-based register. A case-only analysis was carried out and median population density was used to categorize patients into rural or urban environments. We found a significant interaction with population density for marker rs854560 (L55M) in /"ALS"/. | [
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"text_name": "amyotrophic lateral sclerosis"
} | Yes |
19111531 | Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with hypertension in a Tunisian population. | OBJECTIVES: Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilatation and antithrombotic action. Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with hypertension have been reported. In the present study, we examined a possible association between the 27-base pair (bp) repeat polymorphism in intron 4 of the NOS3 gene and hypertension in a sample of the Tunisian population. DESIGN AND METHODS: A total of 295 Tunisian patients with hypertension and 395 healthy controls were included in the study. The NOS3 gene intron 4a4b variable number of tandem repeats polymorphism was analyzed by PCR. RESULTS: A significant differences in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 6.4% for the 4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b genotype and 69.4% for the 4b4b genotype (chi(2)=11.81, p=0.003). The hypertension patient group showed a significant higher frequency of the 4a allele compared to the controls (0.23 vs. 0.16; chi(2)=8.61, p=0.003). The odds ratio of hypertension for 4a vs 4b allele frequencies was statistically significant 1.66 [1.09-2.53] at 95% CI, p=0.01 in males, whereas it was non-significant in females (1.23 [0.84-1.81], p=0.26). CONCLUSION: The present study showed a significant and independent association between the NOS34a4b gene polymorphism (presence of 4a allele) and hypertension in the Tunisian population. | Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with /"hypertension"/ in a Tunisian population. | OBJECTIVES: Nitric oxide (NO) produced by /"endothelial nitric oxide synthase"/ (/"eNOS"/) mediates endothelium-dependent vasodilatation and antithrombotic action. Controversial results regarding the association of /"eNOS"/ gene (/"NOS3"/) polymorphisms with /"hypertension"/ have been reported. In the present study, we examined a possible association between the 27-base pair (bp) repeat polymorphism in intron 4 of the /"NOS3"/ gene and /"hypertension"/ in a sample of the Tunisian population. DESIGN AND METHODS: A total of 295 Tunisian patients with /"hypertension"/ and 395 healthy controls were included in the study. The /"NOS3"/ gene intron 4a4b variable number of tandem repeats polymorphism was analyzed by PCR. RESULTS: A significant differences in genotype distribution and allele frequency was observed between patients and controls. Patients with /"hypertension"/ had a frequency of 6.4% for the 4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b genotype and 69.4% for the 4b4b genotype (chi(2)=11.81, p=0.003). The /"hypertension"/ patient group showed a significant higher frequency of the 4a allele compared to the controls (0.23 vs. 0.16; chi(2)=8.61, p=0.003). The odds ratio of /"hypertension"/ for 4a vs 4b allele frequencies was statistically significant 1.66 [1.09-2.53] at 95% CI, p=0.01 in males, whereas it was non-significant in females (1.23 [0.84-1.81], p=0.26). CONCLUSION: The present study showed a significant and independent association between the NOS34a4b gene polymorphism (presence of 4a allele) and /"hypertension"/ in the Tunisian population. | [
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19115152 | Effects of polymorphism in G2677T/A triallelic region of MDR1 gene in Turkish patients with inflammatory bowel disease. | BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. Crohn's disease and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of P-glycoprotein, encoded by the MDR1 gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the MDR1 gene are thought to be related with the pathogenesis of inflammatory bowel disease. The aim of this study was to investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with inflammatory bowel disease and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed Crohn's disease (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the MDR1 gene. RESULTS: In this study, the frequency of alleles at position 2677 of the MDR1 gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the MDR1 gene was not found to be a risk factor for Crohn's disease or ulcerative colitis. | Effects of polymorphism in G2677T/A triallelic region of /"MDR1"/ gene in Turkish patients with /"inflammatory bowel disease"/. | BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. Crohn's disease and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of /"P-glycoprotein"/, encoded by the /"MDR1"/ gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the /"MDR1"/ gene are thought to be related with the pathogenesis of /"inflammatory bowel disease"/. The aim of this study was to investigate the G2677T/A polymorphism in the /"MDR1"/ gene in Turkish patients with /"inflammatory bowel disease"/ and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed Crohn's disease (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the /"MDR1"/ gene. RESULTS: In this study, the frequency of alleles at position 2677 of the /"MDR1"/ gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the /"MDR1"/ gene was not found to be a risk factor for Crohn's disease or ulcerative colitis. | [
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} | Yes |
19115152 | Effects of polymorphism in G2677T/A triallelic region of MDR1 gene in Turkish patients with inflammatory bowel disease. | BACKGROUND/AIMS: Crohn's disease and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. Crohn's disease and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of P-glycoprotein, encoded by the MDR1 gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the MDR1 gene are thought to be related with the pathogenesis of inflammatory bowel disease. The aim of this study was to investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with inflammatory bowel disease and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed Crohn's disease (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the MDR1 gene. RESULTS: In this study, the frequency of alleles at position 2677 of the MDR1 gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the MDR1 gene was not found to be a risk factor for Crohn's disease or ulcerative colitis. | Effects of polymorphism in G2677T/A triallelic region of /"MDR1"/ gene in Turkish patients with inflammatory bowel disease. | BACKGROUND/AIMS: /"Crohn's disease"/ and ulcerative colitis are both chronic inflammatory disorders of the gastrointestinal tract, the main causes of which remain unknown. /"Crohn's disease"/ and ulcerative colitis are characterized by cell-mediated immune response against the luminal bacteria. It is suggested that expression levels and function of /"P-glycoprotein"/, encoded by the /"MDR1"/ gene, are important for protection of the gut against xenobiotics and bacterial toxins. Therefore, the mutations of the /"MDR1"/ gene are thought to be related with the pathogenesis of inflammatory bowel disease. The aim of this study was to investigate the G2677T/A polymorphism in the /"MDR1"/ gene in Turkish patients with inflammatory bowel disease and a healthy control group. METHODS: In our study, the genotypes of endoscopically or histopathologically diagnosed /"Crohn's disease"/ (n: 35; 14 F, 21 M) and ulcerative colitis (n: 82; 36 F, 46 M) patients and of 70 healthy individuals (39 F, 31 M) were compared. In the patient and control groups, polymerase chain reaction restriction fragment length polymorphism analysis was performed for two polymorphisms (G2677T and G2677A) of the /"MDR1"/ gene. RESULTS: In this study, the frequency of alleles at position 2677 of the /"MDR1"/ gene, which has a triallelic polymorphism, was not found to be significantly different between the patient and the healthy control groups. Moreover, the 2677A allele was not detected in either the patient group or the healthy control group. CONCLUSIONS: In this study, the G2677T/A polymorphism observed in the /"MDR1"/ gene was not found to be a risk factor for /"Crohn's disease"/ or ulcerative colitis. | [
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19115972 | Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? | Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | Should /"HLA-B"/*5701 screening be performed in every ethnic group before starting abacavir? | /"Human leukocyte antigen allele (HLA)-B"/*5701 is associated with abacavir /"hypersensitivity"/. However, the carriage rate of /"HLA-B"/*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, /"HLA-B"/*5701 status was determined by polymerase chain reaction with /"HLA-B"/*5701-specific primers. No patients had the /"HLA-B"/*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir /"hypersensitivity"/ in Koreans. | [
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19115972 | Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? | Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | Should /"HLA-B"/*5701 screening be performed in every ethnic group before starting abacavir? | /"Human leukocyte antigen allele (HLA)-B"/*5701 is associated with abacavir hypersensitivity. However, the carriage rate of /"HLA-B"/*5701 has rarely been studied in Asians. In 534 Korean patients with /"human immunodeficiency virus infection"/, /"HLA-B"/*5701 status was determined by polymerase chain reaction with /"HLA-B"/*5701-specific primers. No patients had the /"HLA-B"/*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | [
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} | Yes |
19115972 | Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? | Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | Should /"HLA-B"/*5701 screening be performed in every ethnic group before starting abacavir? | /"Human leukocyte antigen allele (HLA)-B"/*5701 is associated with abacavir hypersensitivity. However, the carriage rate of /"HLA-B"/*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, /"HLA-B"/*5701 status was determined by polymerase chain reaction with /"HLA-B"/*5701-specific primers. No patients had the /"HLA-B"/*5701 allele (95% confidence interval, 0%-0.7%). This explains the /"paucity"/ of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | [
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19115972 | Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? | Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | Should /"HLA-B"/*5701 screening be performed in every ethnic group before starting abacavir? | /"Human leukocyte antigen allele (HLA)-B"/*5701 is associated with abacavir hypersensitivity. However, the carriage rate of /"HLA-B"/*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, /"HLA-B"/*5701 status was determined by polymerase chain reaction with /"HLA-B"/*5701-specific primers. No patients had the /"HLA-B"/*5701 allele (95% confidence interval, 0%-0.7%). This explains the /"paucity"/ of immunologically confirmed cases of abacavir hypersensitivity in Koreans. | [
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19117570 | PPARgamma promoter polymorphisms and acute coronary syndrome. | BACKGROUND: PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS). METHODS: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls. CONCLUSIONS: The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases. | /"PPARgamma"/ promoter polymorphisms and /"acute coronary syndrome"/. | BACKGROUND: /"PPARgamma"/ (/"PPARg"/) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two /"PPARg"/ common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to /"PPARg"/ coding region, we looked for genetic variations in promoters and their association with /"acute coronary syndrome"/ (/"ACS"/). METHODS: We studied 202 Italian patients with /"ACS"/, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and 2 already published polymorphisms in /"PPARg"/ promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and /"ACS"/ patients (p<0.001); the T allele conferred a protection against /"ACS"/ at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in /"ACS"/ group if compared to healthy controls. CONCLUSIONS: The protective role of 93695C>T polymorphism in /"PPARg"/ promoter in /"ACS"/ suggests that /"PPARg"/ genetic variants may affect the susceptibility to atherosclerotic diseases. | [
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} | {
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} | Yes |
19117570 | PPARgamma promoter polymorphisms and acute coronary syndrome. | BACKGROUND: PPARgamma (PPARg) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two PPARg common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with cardiovascular disease. In this study, in addition to PPARg coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS). METHODS: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and 2 already published polymorphisms in PPARg promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls. CONCLUSIONS: The protective role of 93695C>T polymorphism in PPARg promoter in ACS suggests that PPARg genetic variants may affect the susceptibility to atherosclerotic diseases. | /"PPARgamma"/ promoter polymorphisms and acute coronary syndrome. | BACKGROUND: /"PPARgamma"/ (/"PPARg"/) is a nuclear transcription factor involved in the control of lipid and glucose homeostasis. Two /"PPARg"/ common polymorphisms, Pro12Ala and 161C>T, have been found to be associated with /"cardiovascular disease"/. In this study, in addition to /"PPARg"/ coding region, we looked for genetic variations in promoters and their association with acute coronary syndrome (ACS). METHODS: We studied 202 Italian patients with ACS, and 295 healthy Italian subjects by dHPLC (denaturing high-performance liquid chromatography), heteroduplex analysis and direct sequencing or RFLP (restriction fragment length polymorphism) analysis for screening mutations. RESULTS: We identified 7 new and 2 already published polymorphisms in /"PPARg"/ promoters. The C>T93695 (promoter 4) mutation showed significantly different genotype distribution and allele frequency between controls and ACS patients (p<0.001); the T allele conferred a protection against ACS at both univariate (OR: 0.45, 95% CI 0.29-0.69: p<0.001) and multivariate analysis adjusted for sex, age and traditional cardiovascular risk factors (OR: 0.44, 95% CI 0.25-0.76: p<0.005). Moreover, the 161C>T polymorphism allele frequency (p=0.03) and genotype distribution (p=0.015) resulted to be different in ACS group if compared to healthy controls. CONCLUSIONS: The protective role of 93695C>T polymorphism in /"PPARg"/ promoter in ACS suggests that /"PPARg"/ genetic variants may affect the susceptibility to atherosclerotic diseases. | [
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19122664 | Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. | Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29). | /"Ulcerative colitis"/-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. | /"Ulcerative colitis"/ is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with /"ulcerative colitis"/ and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, /"ulcerative colitis"/ loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the /"IL23R"/ locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29). | [
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19122664 | Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. | Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29). | Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. | Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and /"gastrointestinal bleeding"/. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning /"BTNL2"/ to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29). | [
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19131637 | Associations of genetic variants in ATP-binding cassette A1 and cholesteryl ester transfer protein and differences in lipoprotein subclasses in the multi-ethnic study of atherosclerosis. | BACKGROUND: ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. METHODS: We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. RESULTS: ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. CONCLUSIONS: Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes. | Associations of genetic variants in ATP-binding cassette A1 and /"cholesteryl ester transfer protein"/ and differences in lipoprotein subclasses in the multi-ethnic study of /"atherosclerosis"/. | BACKGROUND: ATP-binding cassette A1 (ABCA1) and /"cholesteryl ester transfer protein"/ (/"CETP"/) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and /"CETP"/ polymorphisms with lipoprotein subclasses have not been extensively studied. METHODS: We genotyped 2 ABCA1 and 5 /"CETP"/ polymorphisms in 999 participants of the Multi-Ethnic Study of /"Atherosclerosis"/ (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. RESULTS: ABCA1 and /"CETP"/ polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The /"CETP"/ TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. CONCLUSIONS: Our study of the influence of ABCA1 and /"CETP"/ genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes. | [
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} | {
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"entity_id": "D050197",
"entity_type": "Disease",
"text_name": "atherosclerosis"
} | Yes |
19131637 | Associations of genetic variants in ATP-binding cassette A1 and cholesteryl ester transfer protein and differences in lipoprotein subclasses in the multi-ethnic study of atherosclerosis. | BACKGROUND: ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. METHODS: We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. RESULTS: ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. CONCLUSIONS: Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes. | Associations of genetic variants in /"ATP-binding cassette A1"/ and cholesteryl ester transfer protein and differences in lipoprotein subclasses in the multi-ethnic study of /"atherosclerosis"/. | BACKGROUND: /"ATP-binding cassette A1"/ (/"ABCA1"/) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of /"ABCA1"/ and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. METHODS: We genotyped 2 /"ABCA1"/ and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of /"Atherosclerosis"/ (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. RESULTS: /"ABCA1"/ and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The /"ABCA1"/ 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. CONCLUSIONS: Our study of the influence of /"ABCA1"/ and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in /"gastric cancer"/ in Costa Rica. | AIM: To evaluate several risk factors for /"gastric cancer"/ (/"GC"/) in Costa Rican regions with contrasting /"GC"/ incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for /"interleukin (IL)-1beta"/ and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 /"GC"/ patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, /"gastric atrophy"/, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with /"GC"/, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing /"GC"/, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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"entity_id": "D013274",
"entity_type": "Disease",
"text_name": "gastric atrophy"
} | Yes |
19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in /"gastric cancer"/ in Costa Rica. | AIM: To evaluate several risk factors for /"gastric cancer"/ (/"GC"/) in Costa Rican regions with contrasting /"GC"/ incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and /"IL-1RN"/ by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 /"GC"/ patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, /"gastric atrophy"/, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), /"IL-1RN"/*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with /"GC"/, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing /"GC"/, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and /"IL-10"/ by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and /"IL-10"/-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of /"H pylori infection"/, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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} | Yes |
19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for /"interleukin (IL)-1beta"/ and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of /"H pylori infection"/, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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} | Yes |
19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and /"IL-1RN"/ by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), /"IL-1RN"/*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of /"H pylori infection"/, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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} | Yes |
19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in /"gastric cancer"/ in Costa Rica. | AIM: To evaluate several risk factors for /"gastric cancer"/ (/"GC"/) in Costa Rican regions with contrasting /"GC"/ incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and /"IL-10"/ by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 /"GC"/ patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, /"gastric atrophy"/, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and /"IL-10"/-592_C/A (OR 3.2, 1.5-6.8) were individually associated with /"GC"/, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing /"GC"/, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and /"IL-10"/ by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed /"strain infection"/) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and /"IL-10"/-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and /"IL-1RN"/ by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed /"strain infection"/) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), /"IL-1RN"/*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for /"interleukin (IL)-1beta"/ and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed /"strain infection"/) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and /"IL-1RN"/ by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed /"strain infection"/) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), /"IL-1RN"/*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19132772 | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | Role of bacterial and genetic factors in gastric cancer in Costa Rica. | AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1beta and /"IL-10"/ by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed /"strain infection"/) were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and /"IL-10"/-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica. | [
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19141225 | [Analysis of the tandem-repeat polymorphisms in DC-SIGNR alleles among drug users population with or without HIV/HCV infection]. | OBJECTIVE: To study the distribution of DC-SIGN/DC-SIGNR alleles among drug user (DUs) populations with or without HIV/HCV infection in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to HIV or HCV and screen out the anti-HIV/HCV gene in Shenzhen. METHODS: All 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for HIV and HCV antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN/DC-SIGNR were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis. RESULTS: Of 500 samples, 97 were found HIV positive, all of which were IDUs and HCV positive. The total positive rate of HCV among all HIV negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among HIV + DUs, there was a higher proportion of patient with the DC-SIGNR 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between HCV + and HCV-DUs and no significant difference between IDUs and other DUs for the DC-SIGNR polymorphism. CONCLUSION: The results might indicate that DC-SIGN/DC-SIGNR polymorphism might not influence the susceptibility to HCV. Genotype 5/6 might probably have a relation with HIV infection, but still need further investigation for the low frequency. | [Analysis of the tandem-repeat polymorphisms in /"DC-SIGNR"/ alleles among drug users population with or without /"HIV/HCV infection"/]. | OBJECTIVE: To study the distribution of DC-SIGN//"DC-SIGNR"/ alleles among drug user (DUs) populations with or without /"HIV/HCV infection"/ in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to /"HIV"/ or HCV and screen out the anti-/"HIV"//HCV gene in Shenzhen. METHODS: All 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for /"HIV"/ and HCV antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN//"DC-SIGNR"/ were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis. RESULTS: Of 500 samples, 97 were found /"HIV"/ positive, all of which were IDUs and HCV positive. The total positive rate of HCV among all /"HIV"/ negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among /"HIV"/ + DUs, there was a higher proportion of patient with the /"DC-SIGNR"/ 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between HCV + and HCV-DUs and no significant difference between IDUs and other DUs for the /"DC-SIGNR"/ polymorphism. CONCLUSION: The results might indicate that DC-SIGN//"DC-SIGNR"/ polymorphism might not influence the susceptibility to HCV. Genotype 5/6 might probably have a relation with /"HIV infection"/, but still need further investigation for the low frequency. | [
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"text_name": "HIV/HCV infection"
} | Yes |
19141225 | [Analysis of the tandem-repeat polymorphisms in DC-SIGNR alleles among drug users population with or without HIV/HCV infection]. | OBJECTIVE: To study the distribution of DC-SIGN/DC-SIGNR alleles among drug user (DUs) populations with or without HIV/HCV infection in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to HIV or HCV and screen out the anti-HIV/HCV gene in Shenzhen. METHODS: All 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for HIV and HCV antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN/DC-SIGNR were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis. RESULTS: Of 500 samples, 97 were found HIV positive, all of which were IDUs and HCV positive. The total positive rate of HCV among all HIV negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among HIV + DUs, there was a higher proportion of patient with the DC-SIGNR 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between HCV + and HCV-DUs and no significant difference between IDUs and other DUs for the DC-SIGNR polymorphism. CONCLUSION: The results might indicate that DC-SIGN/DC-SIGNR polymorphism might not influence the susceptibility to HCV. Genotype 5/6 might probably have a relation with HIV infection, but still need further investigation for the low frequency. | [Analysis of the tandem-repeat polymorphisms in /"DC-SIGNR"/ alleles among drug users population with or without HIV/HCV infection]. | OBJECTIVE: To study the distribution of DC-SIGN//"DC-SIGNR"/ alleles among drug user (DUs) populations with or without HIV/HCV infection in Shenzhen, and to evaluate the role of these alleles in the construction of genetic resistance to HIV or /"HCV"/ and screen out the anti-HIV//"HCV"/ gene in Shenzhen. METHODS: All 500 DU blood samples were collected from Shenzhen Detoxification Center, including 313 from injected drug users (IDUs). All samples were screened for HIV and /"HCV"/ antibody by means of ELISA. The genomic DNA were extracted and amplified by PCR. The neck domain repeat regions of DC-SIGN//"DC-SIGNR"/ were sequenced directly from the PCR products to confirm the amplification for some samples and all positive PCR products were analyzed by agarose gel electrophoresis. RESULTS: Of 500 samples, 97 were found HIV positive, all of which were IDUs and /"HCV"/ positive. The total positive rate of /"HCV"/ among all HIV negative DU was 57.57% (232/403), and it was 63.89% (138/216) among IDUs; in comparing to the 50.26% (94/187) of DUs with other manners there showed significant difference (chi(2) = 7.61, P = 0.0058). Among HIV + DUs, there was a higher proportion of patient with the /"DC-SIGNR"/ 5/6 and 5/8 (Fisher's exact, P = 0.043 and P = 0.034) with statistical significance; there was no statistically significant difference between /"HCV"/ + and /"HCV"/-DUs and no significant difference between IDUs and other DUs for the /"DC-SIGNR"/ polymorphism. CONCLUSION: The results might indicate that DC-SIGN//"DC-SIGNR"/ polymorphism might not influence the susceptibility to /"HCV"/. Genotype 5/6 might probably have a relation with HIV infection, but still need further investigation for the low frequency. | [
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19141695 | Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. | BACKGROUND: Genetic and acquired mechanisms underlying the association of nonalcoholic fatty liver disease (NAFLD) with diabetes are unknown. Glucose-dependent insulinotropic polypeptide (GIP) was recently linked to adipocyte metabolism and obesity-related metabolic disorders, including NAFLD, induced by an excess of saturated fatty acids (SFAs), but its role in vivo, as well as underlying mechanisms, is unknown. We hypothesized that altered GIP secretion may contribute to the pathogenesis of NAFLD. OBJECTIVE: We assessed GIP response to SFA ingestion and its effect on glucose and lipid metabolism and on liver injury in patients with nonalcoholic steatohepatitis (NASH). DESIGN: Thirty-two nonobese, nondiabetic patients with NASH and 32 healthy controls matched for age, body mass index, and sex underwent a 7-d dietary record, an oral-glucose-tolerance test (OGTT), and a high-fat-load test. OGTT-derived indexes of glucose homeostasis were calculated; circulating lipoproteins, total antioxidant status, GIP, adiponectin, resistin, and cytokeratin-18 fragments (markers of hepatocyte apoptosis) after a high-fat meal were assessed. All subjects were genotyped for transcription factor 7-like 2 (TCF7L2) polymorphism. RESULTS: Patients with NASH exhibited a prolonged GIP elevation after fat ingestion. GIP response correlated directly with hepatic steatosis, postprandial resistin, and free fatty acid (FFA) increase and inversely with beta cell function and incretin effect. Dietary polyunsaturated:saturated fatty acid ratio and TCF7L2 polymorphism independently predicted postprandial GIP response. Cytokeratin-18 fragments increased significantly postprandially in both groups but more consistently in patients with NASH; their increase was predicted by postprandial adiponectin and FFA responses. CONCLUSIONS: GIP response to SFA ingestion is prolonged in nondiabetic patients with NASH and is correlated with liver disease, an unfavorable dynamic adipokine profile, and beta cell dysfunction, which provides a rationale for GIP antagonism in these subjects. | Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of /"fatty liver"/. | BACKGROUND: Genetic and acquired mechanisms underlying the association of nonalcoholic fatty liver disease (NAFLD) with diabetes are unknown. Glucose-dependent insulinotropic polypeptide (GIP) was recently linked to adipocyte metabolism and obesity-related metabolic disorders, including NAFLD, induced by an excess of saturated fatty acids (SFAs), but its role in vivo, as well as underlying mechanisms, is unknown. We hypothesized that altered GIP secretion may contribute to the pathogenesis of NAFLD. OBJECTIVE: We assessed GIP response to SFA ingestion and its effect on glucose and lipid metabolism and on liver injury in patients with nonalcoholic steatohepatitis (NASH). DESIGN: Thirty-two nonobese, nondiabetic patients with NASH and 32 healthy controls matched for age, body mass index, and sex underwent a 7-d dietary record, an oral-glucose-tolerance test (OGTT), and a high-fat-load test. OGTT-derived indexes of glucose homeostasis were calculated; circulating lipoproteins, total antioxidant status, GIP, adiponectin, resistin, and cytokeratin-18 fragments (markers of hepatocyte apoptosis) after a high-fat meal were assessed. All subjects were genotyped for /"transcription factor 7-like 2"/ (/"TCF7L2"/) polymorphism. RESULTS: Patients with NASH exhibited a prolonged GIP elevation after fat ingestion. GIP response correlated directly with /"hepatic steatosis"/, postprandial resistin, and free fatty acid (FFA) increase and inversely with beta cell function and incretin effect. Dietary polyunsaturated:saturated fatty acid ratio and /"TCF7L2"/ polymorphism independently predicted postprandial GIP response. Cytokeratin-18 fragments increased significantly postprandially in both groups but more consistently in patients with NASH; their increase was predicted by postprandial adiponectin and FFA responses. CONCLUSIONS: GIP response to SFA ingestion is prolonged in nondiabetic patients with NASH and is correlated with liver disease, an unfavorable dynamic adipokine profile, and beta cell dysfunction, which provides a rationale for GIP antagonism in these subjects. | [
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19141695 | Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. | BACKGROUND: Genetic and acquired mechanisms underlying the association of nonalcoholic fatty liver disease (NAFLD) with diabetes are unknown. Glucose-dependent insulinotropic polypeptide (GIP) was recently linked to adipocyte metabolism and obesity-related metabolic disorders, including NAFLD, induced by an excess of saturated fatty acids (SFAs), but its role in vivo, as well as underlying mechanisms, is unknown. We hypothesized that altered GIP secretion may contribute to the pathogenesis of NAFLD. OBJECTIVE: We assessed GIP response to SFA ingestion and its effect on glucose and lipid metabolism and on liver injury in patients with nonalcoholic steatohepatitis (NASH). DESIGN: Thirty-two nonobese, nondiabetic patients with NASH and 32 healthy controls matched for age, body mass index, and sex underwent a 7-d dietary record, an oral-glucose-tolerance test (OGTT), and a high-fat-load test. OGTT-derived indexes of glucose homeostasis were calculated; circulating lipoproteins, total antioxidant status, GIP, adiponectin, resistin, and cytokeratin-18 fragments (markers of hepatocyte apoptosis) after a high-fat meal were assessed. All subjects were genotyped for transcription factor 7-like 2 (TCF7L2) polymorphism. RESULTS: Patients with NASH exhibited a prolonged GIP elevation after fat ingestion. GIP response correlated directly with hepatic steatosis, postprandial resistin, and free fatty acid (FFA) increase and inversely with beta cell function and incretin effect. Dietary polyunsaturated:saturated fatty acid ratio and TCF7L2 polymorphism independently predicted postprandial GIP response. Cytokeratin-18 fragments increased significantly postprandially in both groups but more consistently in patients with NASH; their increase was predicted by postprandial adiponectin and FFA responses. CONCLUSIONS: GIP response to SFA ingestion is prolonged in nondiabetic patients with NASH and is correlated with liver disease, an unfavorable dynamic adipokine profile, and beta cell dysfunction, which provides a rationale for GIP antagonism in these subjects. | Prolonged saturated fat-induced, /"glucose-dependent insulinotropic polypeptide"/ elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. | BACKGROUND: Genetic and acquired mechanisms underlying the association of nonalcoholic fatty liver disease (NAFLD) with diabetes are unknown. /"Glucose-dependent insulinotropic polypeptide"/ (/"GIP"/) was recently linked to adipocyte metabolism and obesity-related /"metabolic disorders"/, including NAFLD, induced by an excess of saturated fatty acids (SFAs), but its role in vivo, as well as underlying mechanisms, is unknown. We hypothesized that altered /"GIP"/ secretion may contribute to the pathogenesis of NAFLD. OBJECTIVE: We assessed /"GIP"/ response to SFA ingestion and its effect on glucose and lipid metabolism and on liver injury in patients with nonalcoholic steatohepatitis (NASH). DESIGN: Thirty-two nonobese, nondiabetic patients with NASH and 32 healthy controls matched for age, body mass index, and sex underwent a 7-d dietary record, an oral-glucose-tolerance test (OGTT), and a high-fat-load test. OGTT-derived indexes of glucose homeostasis were calculated; circulating lipoproteins, total antioxidant status, /"GIP"/, adiponectin, resistin, and cytokeratin-18 fragments (markers of hepatocyte apoptosis) after a high-fat meal were assessed. All subjects were genotyped for transcription factor 7-like 2 (TCF7L2) polymorphism. RESULTS: Patients with NASH exhibited a prolonged /"GIP"/ elevation after fat ingestion. /"GIP"/ response correlated directly with hepatic steatosis, postprandial resistin, and free fatty acid (FFA) increase and inversely with beta cell function and incretin effect. Dietary polyunsaturated:saturated fatty acid ratio and TCF7L2 polymorphism independently predicted postprandial /"GIP"/ response. Cytokeratin-18 fragments increased significantly postprandially in both groups but more consistently in patients with NASH; their increase was predicted by postprandial adiponectin and FFA responses. CONCLUSIONS: /"GIP"/ response to SFA ingestion is prolonged in nondiabetic patients with NASH and is correlated with liver disease, an unfavorable dynamic adipokine profile, and beta cell dysfunction, which provides a rationale for /"GIP"/ antagonism in these subjects. | [
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19141698 | Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia. | The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease. | Polyunsaturated fatty acids modulate the effect of /"TCF7L2"/ gene variants on postprandial /"lipemia"/. | The /"transcription factor 7-like 2"/ (/"TCF7L2"/) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the /"TCF7L2"/ locus on postprandial /"lipemia"/ and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the /"TCF7L2"/ rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease. | [
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19141698 | Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia. | The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease. | Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia. | The transcription factor 7-like 2 (TCF7L2) has been recently associated with /"diabetes"/ risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and /"PUFA"/ intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a /"PUFA"/ intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-/"PUFA"/ intake group. Moreover, these significant interactions were due exclusively to (n-6) /"PUFA"/ intake. In summary, high (n-6) /"PUFA"/ intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, /"diabetes"/, and cardiovascular disease. | [
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19145484 | Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. | Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to influence breast cancer risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case-control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), Apa1 (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of breast cancer (ff vs. FF: OR = 1.15, 95% CI = 1.03-1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03-1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and breast cancer in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04-1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04-1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, Apa1 and Taq1 variants and breast cancer risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for breast cancer especially in European population. | Fok1 polymorphism of /"vitamin D receptor"/ gene contributes to /"breast cancer"/ susceptibility: a meta-analysis. | Several polymorphisms in the /"vitamin D receptor"/ (/"VDR"/) gene have been reported to influence /"breast cancer"/ risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case-control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), Apa1 (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of /"breast cancer"/ (ff vs. FF: OR = 1.15, 95% CI = 1.03-1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03-1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and /"breast cancer"/ in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04-1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04-1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, Apa1 and Taq1 variants and /"breast cancer"/ risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for /"breast cancer"/ especially in European population. | [
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19145484 | Fok1 polymorphism of vitamin D receptor gene contributes to breast cancer susceptibility: a meta-analysis. | Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to influence breast cancer risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case-control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), Apa1 (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of breast cancer (ff vs. FF: OR = 1.15, 95% CI = 1.03-1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03-1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and breast cancer in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04-1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04-1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, Apa1 and Taq1 variants and breast cancer risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for breast cancer especially in European population. | Fok1 polymorphism of vitamin D receptor gene contributes to /"breast cancer"/ susceptibility: a meta-analysis. | Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to influence /"breast cancer"/ risk. However, the published findings have been conflicting. We conducted a meta-analysis of 21 case-control studies with Fok1 (eight studies with 5,284 cases and 7,500 controls), Bsm1 (14 studies with 5,498 cases and 7,943 controls), /"Apa1"/ (four studies with 1,138 cases and 7,943 controls), Taq1 (10 studies with 4,459 cases and 5,485 controls) polymorphisms. The results showed Fok1 polymorphism was associated with an overall significantly increased risk of /"breast cancer"/ (ff vs. FF: OR = 1.15, 95% CI = 1.03-1.28; the recessive model ff vs. Ff + FF: OR = 1.14, 95% CI = 1.03-1.26). In subgroup analysis, a significant association was evident between Fok1 polymorphism and /"breast cancer"/ in European population (ff vs. FF: OR = 1.16, 95% CI = 1.04-1.30; the recessive model ff vs. Ff + FF: OR = 1.15, 95% CI = 1.04-1.28). There was no between-study heterogeneity in any of these analyses. No significant associations were observed between the Bsm1, /"Apa1"/ and Taq1 variants and /"breast cancer"/ risk. So, the current meta-analysis shows that Fok1 may be a susceptibility biomarker for /"breast cancer"/ especially in European population. | [
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19147210 | The haplotype of two FSHR polymorphisms in ovarian cancer--a potential role of ethnology in risk modification. | OBJECTIVES: The precise role of gonadotropins in the carcinogenesis of epithelial ovarian cancer remains uncertain. Recently, the haplotype of two single nucleotide polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), has been described as a risk factor for ovarian cancer in Chinese women. In this study we investigated the impact of this haplotype regarding the risk to develop ovarian cancer as well as possible effects upon the clinical course in a Caucasian patient sample. SUBJECTS AND METHODS: Determination of genotypes in 115 patients with primary epithelial ovarian cancer and 115 age-matched controls was performed by Pyrosequencing for Thr307Ala and by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for Asn680Ser. RESULTS: Analysis of the genotypes revealed almost complete linkage disequilibrium of both SNPs. The distribution of genotypes was not statistically significant different between ovarian cancer patients and age-matched controls. Clinical parameters such as overall survival, CA12-5 elevation at primary diagnosis, age at diagnosis, FIGO stage, grading, and platinum resistance were not statistically significantly different regarding genotypes. CONCLUSIONS: We could not confirm the FSHR Ala307-Ser680 haplotype as a risk factor for epithelial ovarian cancer in Caucasian women. Hence, the modification of tumor risk may be affected by the ethnology of the patient collective. We could not find any associations of clinical parameters or course of the disease with the different genotypes. | The haplotype of two /"FSHR"/ polymorphisms in /"ovarian cancer"/--a potential role of ethnology in risk modification. | OBJECTIVES: The precise role of gonadotropins in the /"carcinogenesis of epithelial ovarian cancer"/ remains uncertain. Recently, the haplotype of two single nucleotide polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), has been described as a risk factor for /"ovarian cancer"/ in Chinese women. In this study we investigated the impact of this haplotype regarding the risk to develop /"ovarian cancer"/ as well as possible effects upon the clinical course in a Caucasian patient sample. SUBJECTS AND METHODS: Determination of genotypes in 115 patients with /"primary epithelial ovarian cancer"/ and 115 age-matched controls was performed by Pyrosequencing for Thr307Ala and by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for Asn680Ser. RESULTS: Analysis of the genotypes revealed almost complete linkage disequilibrium of both SNPs. The distribution of genotypes was not statistically significant different between /"ovarian cancer"/ patients and age-matched controls. Clinical parameters such as overall survival, CA12-5 elevation at primary diagnosis, age at diagnosis, FIGO stage, grading, and platinum resistance were not statistically significantly different regarding genotypes. CONCLUSIONS: We could not confirm the /"FSHR"/ Ala307-Ser680 haplotype as a risk factor for /"epithelial ovarian cancer"/ in Caucasian women. Hence, the modification of tumor risk may be affected by the ethnology of the patient collective. We could not find any associations of clinical parameters or course of the disease with the different genotypes. | [
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19147210 | The haplotype of two FSHR polymorphisms in ovarian cancer--a potential role of ethnology in risk modification. | OBJECTIVES: The precise role of gonadotropins in the carcinogenesis of epithelial ovarian cancer remains uncertain. Recently, the haplotype of two single nucleotide polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), has been described as a risk factor for ovarian cancer in Chinese women. In this study we investigated the impact of this haplotype regarding the risk to develop ovarian cancer as well as possible effects upon the clinical course in a Caucasian patient sample. SUBJECTS AND METHODS: Determination of genotypes in 115 patients with primary epithelial ovarian cancer and 115 age-matched controls was performed by Pyrosequencing for Thr307Ala and by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for Asn680Ser. RESULTS: Analysis of the genotypes revealed almost complete linkage disequilibrium of both SNPs. The distribution of genotypes was not statistically significant different between ovarian cancer patients and age-matched controls. Clinical parameters such as overall survival, CA12-5 elevation at primary diagnosis, age at diagnosis, FIGO stage, grading, and platinum resistance were not statistically significantly different regarding genotypes. CONCLUSIONS: We could not confirm the FSHR Ala307-Ser680 haplotype as a risk factor for epithelial ovarian cancer in Caucasian women. Hence, the modification of tumor risk may be affected by the ethnology of the patient collective. We could not find any associations of clinical parameters or course of the disease with the different genotypes. | The haplotype of two /"FSHR"/ polymorphisms in ovarian cancer--a potential role of ethnology in risk modification. | OBJECTIVES: The precise role of gonadotropins in the carcinogenesis of epithelial ovarian cancer remains uncertain. Recently, the haplotype of two single nucleotide polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), has been described as a risk factor for ovarian cancer in Chinese women. In this study we investigated the impact of this haplotype regarding the risk to develop ovarian cancer as well as possible effects upon the clinical course in a Caucasian patient sample. SUBJECTS AND METHODS: Determination of genotypes in 115 patients with primary epithelial ovarian cancer and 115 age-matched controls was performed by Pyrosequencing for Thr307Ala and by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for Asn680Ser. RESULTS: Analysis of the genotypes revealed almost complete linkage disequilibrium of both SNPs. The distribution of genotypes was not statistically significant different between ovarian cancer patients and age-matched controls. Clinical parameters such as overall survival, CA12-5 elevation at primary diagnosis, age at diagnosis, FIGO stage, grading, and platinum resistance were not statistically significantly different regarding genotypes. CONCLUSIONS: We could not confirm the /"FSHR"/ Ala307-Ser680 haplotype as a risk factor for epithelial ovarian cancer in Caucasian women. Hence, the modification of /"tumor"/ risk may be affected by the ethnology of the patient collective. We could not find any associations of clinical parameters or course of the disease with the different genotypes. | [
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19152006 | New genetic evidence for involvement of the dopamine system in migraine with aura. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to migraine with aura (MA), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German migraine with aura case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 MA cases and 272 controls, three genes-DBH, DRD2 and SLC6A3-were chosen to proceed to additional genotyping of 380 MA cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 MA patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with DBH and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of migraine with aura. | New genetic evidence for involvement of the dopamine system in /"migraine with aura"/. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to /"migraine with aura"/ (/"MA"/), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German /"migraine with aura"/ case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 /"MA"/ cases and 272 controls, three genes-/"DBH"/, DRD2 and SLC6A3-were chosen to proceed to additional genotyping of 380 /"MA"/ cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 /"MA"/ patients and 650 controls. Three of these SNPs [rs2097629 in /"DBH"/ (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with /"DBH"/ and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the /"dopamine-beta hydroxylase"/ and dopamine transporter genes-to the pathogenesis of /"migraine with aura"/. | [
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19152006 | New genetic evidence for involvement of the dopamine system in migraine with aura. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to migraine with aura (MA), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German migraine with aura case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 MA cases and 272 controls, three genes-DBH, DRD2 and SLC6A3-were chosen to proceed to additional genotyping of 380 MA cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 MA patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with DBH and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of migraine with aura. | New genetic evidence for involvement of the dopamine system in /"migraine with aura"/. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to /"migraine with aura"/ (/"MA"/), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German /"migraine with aura"/ case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 /"MA"/ cases and 272 controls, three genes-DBH, /"DRD2"/ and SLC6A3-were chosen to proceed to additional genotyping of 380 /"MA"/ cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 /"MA"/ patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in /"DRD2"/ (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with /"DRD2"/, but supported the associations with DBH and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of /"migraine with aura"/. | [
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19152006 | New genetic evidence for involvement of the dopamine system in migraine with aura. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to migraine with aura (MA), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German migraine with aura case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 MA cases and 272 controls, three genes-DBH, DRD2 and SLC6A3-were chosen to proceed to additional genotyping of 380 MA cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 MA patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with DBH and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of migraine with aura. | New genetic evidence for involvement of the dopamine system in /"migraine with aura"/. | In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to /"migraine with aura"/ (/"MA"/), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German /"migraine with aura"/ case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 /"MA"/ cases and 272 controls, three genes-DBH, DRD2 and /"SLC6A3"/-were chosen to proceed to additional genotyping of 380 /"MA"/ cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 /"MA"/ patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in /"SLC6A3"/ (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with DBH and /"SLC6A3"/. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of /"migraine with aura"/. | [
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"entity_id": "D020325",
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"text_name": "migraine with aura"
} | Yes |
19161138 | Mutation analysis of the myocyte enhancer factor 2A gene (MEF2A) in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy. | Mutation analysis of the /"myocyte enhancer factor 2A"/ gene (/"MEF2A"/) in patients with /"left ventricular hypertrophy"//hypertrophic cardiomyopathy. | [
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} | Yes |
||
19161138 | Mutation analysis of the myocyte enhancer factor 2A gene (MEF2A) in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy. | Mutation analysis of the /"myocyte enhancer factor 2A"/ gene (/"MEF2A"/) in patients with left ventricular hypertrophy//"hypertrophic cardiomyopathy"/. | [
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} | Yes |
||
19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN//"AKT"//mTOR pathway are associated with clinical outcomes in /"esophageal cancer"/ patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-/"akt"/ murine thymoma viral oncogene homolog (/"AKT"/), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in /"esophageal cancer"/ patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, /"AKT1"/, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in /"AKT1"/ and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of /"AKT"/ adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in /"AKT1"/, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for /"AKT1"/:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the /"PI3K"//PTEN/AKT/mTOR pathway are associated with clinical outcomes in /"esophageal cancer"/ patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in /"esophageal cancer"/ patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in /"PIK3CA"/, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K//"PTEN"//AKT/mTOR pathway are associated with clinical outcomes in /"esophageal cancer"/ patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (/"PTEN"/), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in /"esophageal cancer"/ patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, /"PTEN"/, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by /"PTEN"/ genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in /"esophageal cancer"/ patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in /"esophageal cancer"/ patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, /"AKT2"/, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and /"AKT2"/ (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, /"AKT2"/, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--/"AKT2"/ and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in /"esophageal cancer"/ patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and /"mammalian target of rapamycin"/ (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in /"esophageal cancer"/ patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and /"FRAP1"/ (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and /"FRAP1"/ were associated with survival. Patients homozygous for either of the /"FRAP1"/ SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and /"FRAP1"/--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN/AKT//"mTOR"/ pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (/"mTOR"/) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding /"mTOR"/) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of /"death"/. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The /"phosphoinositide-3-kinase"/ (/"PI3K"/), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or /"squamous cell carcinoma"/ who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K//"PTEN"//AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (/"PTEN"/), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or /"squamous cell carcinoma"/ who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, /"PTEN"/, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by /"PTEN"/ genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the /"PI3K"//PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with /"adenocarcinoma"/ or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in /"PIK3CA"/, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19164214 | Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | Genetic variations in the PI3K/PTEN//"AKT"//mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. | PURPOSE: The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-/"akt"/ murine thymoma viral oncogene homolog (/"AKT"/), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or /"squamous cell carcinoma"/ who have undergone chemoradiotherapy and surgery. PATIENTS AND METHODS: Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, /"AKT1"/, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. RESULTS: We observed an increased recurrence risk with genetic variations in /"AKT1"/ and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of /"AKT"/ adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in /"AKT1"/, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes--AKT2 and FRAP1--were associated with a poor treatment response, while a better response was associated with heterozygosity for /"AKT1"/:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). CONCLUSION: These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen. | [
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19173862 | [Study on the relationship between polymorphisms of XPA gene and susceptibility of esophageal cancer]. | OBJECTIVE: To explore the relationships between the polymorphisms of xeroderma pigmentosum A (XPA) and the susceptibility of esophageal cancer (EC), as well as its interaction with environmental factors-gene in Changzhi area, Shanxi province. METHODS: A case-control study was conducted, including 196 cases of EC and 201 controls. XPA 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of EC was significantly degraded in the individuals who had been carrying the XPA heterozygote (A/G) and mutation genotype (G/G), compared to those with wild genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56), respectively. There was negative interaction between XPA 23G mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77). CONCLUSION: Genetic polymorphism in the XPA 23G might be associated with esophageal cancer in Changzhi area, and there was a negative action between XPA predisposing genotype and the consumption of pickled food. | [Study on the relationship between polymorphisms of /"XPA"/ gene and susceptibility of /"esophageal cancer"/]. | OBJECTIVE: To explore the relationships between the polymorphisms of xeroderma pigmentosum A (/"XPA"/) and the susceptibility of /"esophageal cancer"/ (/"EC"/), as well as its interaction with environmental factors-gene in Changzhi area, Shanxi province. METHODS: A case-control study was conducted, including 196 cases of /"EC"/ and 201 controls. /"XPA"/ 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of /"EC"/ was significantly degraded in the individuals who had been carrying the /"XPA"/ heterozygote (A/G) and mutation genotype (G/G), compared to those with wild genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56), respectively. There was negative interaction between /"XPA"/ 23G mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77). CONCLUSION: Genetic polymorphism in the /"XPA"/ 23G might be associated with /"esophageal cancer"/ in Changzhi area, and there was a negative action between /"XPA"/ predisposing genotype and the consumption of pickled food. | [
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19173862 | [Study on the relationship between polymorphisms of XPA gene and susceptibility of esophageal cancer]. | OBJECTIVE: To explore the relationships between the polymorphisms of xeroderma pigmentosum A (XPA) and the susceptibility of esophageal cancer (EC), as well as its interaction with environmental factors-gene in Changzhi area, Shanxi province. METHODS: A case-control study was conducted, including 196 cases of EC and 201 controls. XPA 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of EC was significantly degraded in the individuals who had been carrying the XPA heterozygote (A/G) and mutation genotype (G/G), compared to those with wild genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56), respectively. There was negative interaction between XPA 23G mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77). CONCLUSION: Genetic polymorphism in the XPA 23G might be associated with esophageal cancer in Changzhi area, and there was a negative action between XPA predisposing genotype and the consumption of pickled food. | [Study on the relationship between polymorphisms of /"XPA"/ gene and susceptibility of esophageal cancer]. | OBJECTIVE: To explore the relationships between the polymorphisms of /"xeroderma pigmentosum"/ A (/"XPA"/) and the susceptibility of esophageal cancer (EC), as well as its interaction with environmental factors-gene in Changzhi area, Shanxi province. METHODS: A case-control study was conducted, including 196 cases of EC and 201 controls. /"XPA"/ 23G polymorphisms were determined with polymerase chain-restriction on fragment length polymorphism (PCR-RFLP). RESULTS: The risk of EC was significantly degraded in the individuals who had been carrying the /"XPA"/ heterozygote (A/G) and mutation genotype (G/G), compared to those with wild genotype (chi2 = 16.21, P < 0.01) and the ORs were 0.58 (0.37-0.91) and 0.32 (0.18-0.56), respectively. There was negative interaction between /"XPA"/ 23G mutation genotype and the consumption of pickled food (S = 0.04, API= -0.77). CONCLUSION: Genetic polymorphism in the /"XPA"/ 23G might be associated with esophageal cancer in Changzhi area, and there was a negative action between /"XPA"/ predisposing genotype and the consumption of pickled food. | [
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} | No |
19190165 | Rad50 c.687delT does not contribute significantly to familial breast cancer in a French population. | Mutations in DNA repair genes are known for their association with hereditary breast cancer. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in ATM or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with breast cancer risk: heterozygosity for deleterious mutations in components of the Rad50-Mre11-Nbs1 complex seems to predispose to breast cancer. In particular, the c.687delT mutation in Rad50 conferred an odds ratio of 4.3 for the risk of breast cancer in a study of Finnish breast cancer families. To explore the contribution of this mutation to breast cancer in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 familial breast cancer cases and 513 controls with no personal or familial history of breast cancer. Rad50 was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make Rad50 a significant breast cancer risk factor in certain populations, it is not a factor in others. | /"Rad50"/ c.687delT does not contribute significantly to /"familial breast cancer"/ in a French population. | Mutations in DNA repair genes are known for their association with /"hereditary breast cancer"/. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in ATM or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with /"breast cancer"/ risk: heterozygosity for deleterious mutations in components of the /"Rad50"/-Mre11-Nbs1 complex seems to predispose to /"breast cancer"/. In particular, the c.687delT mutation in /"Rad50"/ conferred an odds ratio of 4.3 for the risk of /"breast cancer"/ in a study of Finnish /"breast cancer"/ families. To explore the contribution of this mutation to /"breast cancer"/ in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 /"familial breast cancer"/ cases and 513 controls with no personal or familial history of /"breast cancer"/. /"Rad50"/ was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make /"Rad50"/ a significant /"breast cancer"/ risk factor in certain populations, it is not a factor in others. | [
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19190165 | Rad50 c.687delT does not contribute significantly to familial breast cancer in a French population. | Mutations in DNA repair genes are known for their association with hereditary breast cancer. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in ATM or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with breast cancer risk: heterozygosity for deleterious mutations in components of the Rad50-Mre11-Nbs1 complex seems to predispose to breast cancer. In particular, the c.687delT mutation in Rad50 conferred an odds ratio of 4.3 for the risk of breast cancer in a study of Finnish breast cancer families. To explore the contribution of this mutation to breast cancer in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 familial breast cancer cases and 513 controls with no personal or familial history of breast cancer. Rad50 was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make Rad50 a significant breast cancer risk factor in certain populations, it is not a factor in others. | Rad50 c.687delT does not contribute significantly to /"familial breast cancer"/ in a French population. | Mutations in DNA repair genes are known for their association with /"hereditary breast cancer"/. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in /"ATM"/ or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with /"breast cancer"/ risk: heterozygosity for deleterious mutations in components of the Rad50-Mre11-Nbs1 complex seems to predispose to /"breast cancer"/. In particular, the c.687delT mutation in Rad50 conferred an odds ratio of 4.3 for the risk of /"breast cancer"/ in a study of Finnish /"breast cancer"/ families. To explore the contribution of this mutation to /"breast cancer"/ in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 /"familial breast cancer"/ cases and 513 controls with no personal or familial history of /"breast cancer"/. Rad50 was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make Rad50 a significant /"breast cancer"/ risk factor in certain populations, it is not a factor in others. | [
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19190538 | Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics. | Rett Syndrome (RTT) is caused in more than 60% of cases by nonsense mutations in the MECP2 gene. So far, no curative therapy for RTT has become available. In other genetic disorders, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to RTT. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring MECP2 nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the MECP2 gene can be achieved in vitro with efficiency comparable with that seen in other disorders. | Suppression of nonsense mutations in /"Rett syndrome"/ by aminoglycoside antibiotics. | /"Rett Syndrome"/ (/"RTT"/) is caused in more than 60% of cases by nonsense mutations in the /"MECP2"/ gene. So far, no curative therapy for /"RTT"/ has become available. In other genetic disorders, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to /"RTT"/. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring /"MECP2"/ nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the /"MECP2"/ gene can be achieved in vitro with efficiency comparable with that seen in other disorders. | [
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19190538 | Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics. | Rett Syndrome (RTT) is caused in more than 60% of cases by nonsense mutations in the MECP2 gene. So far, no curative therapy for RTT has become available. In other genetic disorders, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to RTT. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring MECP2 nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the MECP2 gene can be achieved in vitro with efficiency comparable with that seen in other disorders. | Suppression of nonsense mutations in Rett syndrome by aminoglycoside antibiotics. | Rett Syndrome (RTT) is caused in more than 60% of cases by nonsense mutations in the /"MECP2"/ gene. So far, no curative therapy for RTT has become available. In other /"genetic disorders"/, it has been shown that aminoglycosides can cause a read-through of nonsense mutations with an efficiency of up to 20%. The aim of this study was to evaluate if this therapeutic concept is applicable to RTT. HeLa cells were transfected with eukaryotic expression vectors carrying mutant alleles of frequently occurring /"MECP2"/ nonsense mutations that were N-terminally fused to a FLAG tag. Transfected cells were incubated 24 h in the presence of gentamicin. The expression of full-length protein was analyzed by Western blotting and immunofluorescent cell staining. In the presence of gentamicin a read-through varying between 10 and 21.8% was found, depending on the nucleotide sequence context of the nonsense mutations. The full-length protein was located correctly in the nucleus. We have shown that aminoglycoside-mediated read-through of nonsense mutations in the /"MECP2"/ gene can be achieved in vitro with efficiency comparable with that seen in other disorders. | [
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19191329 | Increasing the number of diagnostic mutations in malignant hyperthermia. | Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on ryanodine receptor type 1 (RYR1) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with MH diagnosis. In approximately 50% of MH cases a causative RYR1 mutation was found. Molecular genetic testing based on RYR1 mutations for MH diagnosis is challenging, because the causative mutations, most of which are private, are distributed throughout the RYR1 gene. A more comprehensive genetic testing procedure is needed. Therefore, we aim to expand the genetic information related to MH and to evaluate the effect of mutations on the MH phenotype. Performing an in-depth mutation screening of the RYR1 transcript sequence in 36 unrelated MH susceptible (MHS) patients, we identified 17 novel, five rare, and eight non-disease-causing variants in 23 patients. The 13 remaining MHS patients presented no known variants, neither in RYR1 nor in the CACNA1S binding regions to RYR1. The 17 novel variants were found to affect highly conserved amino acids and were absent in 100 controls. Excellent genotype-phenotype correlations were found by investigating 21 MHS families-a total of 186 individuals. Epstein-Barr virus (EBV) lymphoblastoid cells carrying four of these novel mutations showed abnormal calcium homeostasis. The results of this study contribute to the establishment of a robust genetic testing procedure for MH diagnosis. | Increasing the number of diagnostic mutations in malignant hyperthermia. | /"Malignant hyperthermia"/ (/"MH"/) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on /"ryanodine receptor type 1"/ (/"RYR1"/) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with /"MH"/ diagnosis. In approximately 50% of /"MH"/ cases a causative /"RYR1"/ mutation was found. Molecular genetic testing based on /"RYR1"/ mutations for /"MH"/ diagnosis is challenging, because the causative mutations, most of which are private, are distributed throughout the /"RYR1"/ gene. A more comprehensive genetic testing procedure is needed. Therefore, we aim to expand the genetic information related to /"MH"/ and to evaluate the effect of mutations on the /"MH"/ phenotype. Performing an in-depth mutation screening of the /"RYR1"/ transcript sequence in 36 unrelated /"MH susceptible"/ (/"MHS"/) patients, we identified 17 novel, five rare, and eight non-disease-causing variants in 23 patients. The 13 remaining /"MHS"/ patients presented no known variants, neither in /"RYR1"/ nor in the CACNA1S binding regions to /"RYR1"/. The 17 novel variants were found to affect highly conserved amino acids and were absent in 100 controls. Excellent genotype-phenotype correlations were found by investigating 21 /"MHS"/ families-a total of 186 individuals. Epstein-Barr virus (EBV) lymphoblastoid cells carrying four of these novel mutations showed abnormal calcium homeostasis. The results of this study contribute to the establishment of a robust genetic testing procedure for /"MH"/ diagnosis. | [
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19191329 | Increasing the number of diagnostic mutations in malignant hyperthermia. | Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on ryanodine receptor type 1 (RYR1) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with MH diagnosis. In approximately 50% of MH cases a causative RYR1 mutation was found. Molecular genetic testing based on RYR1 mutations for MH diagnosis is challenging, because the causative mutations, most of which are private, are distributed throughout the RYR1 gene. A more comprehensive genetic testing procedure is needed. Therefore, we aim to expand the genetic information related to MH and to evaluate the effect of mutations on the MH phenotype. Performing an in-depth mutation screening of the RYR1 transcript sequence in 36 unrelated MH susceptible (MHS) patients, we identified 17 novel, five rare, and eight non-disease-causing variants in 23 patients. The 13 remaining MHS patients presented no known variants, neither in RYR1 nor in the CACNA1S binding regions to RYR1. The 17 novel variants were found to affect highly conserved amino acids and were absent in 100 controls. Excellent genotype-phenotype correlations were found by investigating 21 MHS families-a total of 186 individuals. Epstein-Barr virus (EBV) lymphoblastoid cells carrying four of these novel mutations showed abnormal calcium homeostasis. The results of this study contribute to the establishment of a robust genetic testing procedure for MH diagnosis. | Increasing the number of diagnostic mutations in malignant hyperthermia. | Malignant hyperthermia (MH) is an /"autosomal dominant disorder"/ characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on /"ryanodine receptor type 1"/ (/"RYR1"/) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with MH diagnosis. In approximately 50% of MH cases a causative /"RYR1"/ mutation was found. Molecular genetic testing based on /"RYR1"/ mutations for MH diagnosis is challenging, because the causative mutations, most of which are private, are distributed throughout the /"RYR1"/ gene. A more comprehensive genetic testing procedure is needed. Therefore, we aim to expand the genetic information related to MH and to evaluate the effect of mutations on the MH phenotype. Performing an in-depth mutation screening of the /"RYR1"/ transcript sequence in 36 unrelated MH susceptible (MHS) patients, we identified 17 novel, five rare, and eight non-disease-causing variants in 23 patients. The 13 remaining MHS patients presented no known variants, neither in /"RYR1"/ nor in the CACNA1S binding regions to /"RYR1"/. The 17 novel variants were found to affect highly conserved amino acids and were absent in 100 controls. Excellent genotype-phenotype correlations were found by investigating 21 MHS families-a total of 186 individuals. Epstein-Barr virus (EBV) lymphoblastoid cells carrying four of these novel mutations showed abnormal calcium homeostasis. The results of this study contribute to the establishment of a robust genetic testing procedure for MH diagnosis. | [
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19210878 | Contribution of the R620W polymorphism of protein tyrosine phosphatase non-receptor 22 to systemic lupus erythematosus in Poland. | The protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with systemic lupus erythematosus (SLE) and other autoimmune diseases. However, its contribution to SLE has been found to be disputable. We therefore examined the association of PTPN22 1858 C>T polymorphism with susceptibility to SLE in the Polish population, among patients with SLE (n=150) and controls (n=300). We found a contribution of the PTPN22 1858 C>T polymorphism to the incidence of SLE. Women with the PTPN22 TT and PTPN22 CT genotypes displayed a 2.016-fold increased risk of SLE (95% CI=1.324 - 3.070, P=0.0014). However, we did not observe an increased risk for the homozygous PTPN22 TT genotype OR= 2.552 (95% CI=0.6748-9.64, p=0.1675). Our results confirm an association of the 1858 C>T polymorphism of the PTPN22 gene with SLE, which was previously observed in other populations. | Contribution of the R620W polymorphism of /"protein tyrosine phosphatase non-receptor 22"/ to /"systemic lupus erythematosus"/ in Poland. | The /"protein tyrosine phosphatase non-receptor 22"/ (/"PTPN22"/) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with /"systemic lupus erythematosus"/ (/"SLE"/) and other autoimmune diseases. However, its contribution to /"SLE"/ has been found to be disputable. We therefore examined the association of /"PTPN22"/ 1858 C>T polymorphism with susceptibility to /"SLE"/ in the Polish population, among patients with /"SLE"/ (n=150) and controls (n=300). We found a contribution of the /"PTPN22"/ 1858 C>T polymorphism to the incidence of /"SLE"/. Women with the /"PTPN22"/ TT and /"PTPN22"/ CT genotypes displayed a 2.016-fold increased risk of /"SLE"/ (95% CI=1.324 - 3.070, P=0.0014). However, we did not observe an increased risk for the homozygous /"PTPN22"/ TT genotype OR= 2.552 (95% CI=0.6748-9.64, p=0.1675). Our results confirm an association of the 1858 C>T polymorphism of the /"PTPN22"/ gene with /"SLE"/, which was previously observed in other populations. | [
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} | Yes |
19210878 | Contribution of the R620W polymorphism of protein tyrosine phosphatase non-receptor 22 to systemic lupus erythematosus in Poland. | The protein tyrosine phosphatase non-receptor 22 (PTPN22) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with systemic lupus erythematosus (SLE) and other autoimmune diseases. However, its contribution to SLE has been found to be disputable. We therefore examined the association of PTPN22 1858 C>T polymorphism with susceptibility to SLE in the Polish population, among patients with SLE (n=150) and controls (n=300). We found a contribution of the PTPN22 1858 C>T polymorphism to the incidence of SLE. Women with the PTPN22 TT and PTPN22 CT genotypes displayed a 2.016-fold increased risk of SLE (95% CI=1.324 - 3.070, P=0.0014). However, we did not observe an increased risk for the homozygous PTPN22 TT genotype OR= 2.552 (95% CI=0.6748-9.64, p=0.1675). Our results confirm an association of the 1858 C>T polymorphism of the PTPN22 gene with SLE, which was previously observed in other populations. | Contribution of the R620W polymorphism of /"protein tyrosine phosphatase non-receptor 22"/ to systemic lupus erythematosus in Poland. | The /"protein tyrosine phosphatase non-receptor 22"/ (/"PTPN22"/) 1858 C>T poly-morphic variant gene (rs2476601) displays an association with systemic lupus erythematosus (SLE) and other /"autoimmune diseases"/. However, its contribution to SLE has been found to be disputable. We therefore examined the association of /"PTPN22"/ 1858 C>T polymorphism with susceptibility to SLE in the Polish population, among patients with SLE (n=150) and controls (n=300). We found a contribution of the /"PTPN22"/ 1858 C>T polymorphism to the incidence of SLE. Women with the /"PTPN22"/ TT and /"PTPN22"/ CT genotypes displayed a 2.016-fold increased risk of SLE (95% CI=1.324 - 3.070, P=0.0014). However, we did not observe an increased risk for the homozygous /"PTPN22"/ TT genotype OR= 2.552 (95% CI=0.6748-9.64, p=0.1675). Our results confirm an association of the 1858 C>T polymorphism of the /"PTPN22"/ gene with SLE, which was previously observed in other populations. | [
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19210888 | Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA. | Role of HLA-DRB1 and /"PTPN22"/ genes in susceptibility to /"juvenile idiopathic arthritis"/ in Hungarian patients. | OBJECTIVE: /"Juvenile idiopathic arthritis"/ (/"JIA"/) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and /"protein tyrosine phosphatase N22"/ (/"PTPN22"/) with /"JIA"/ in Hungarian patients. METHODS: A case-control study including 150 /"Hungarian JIA"/ patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and /"PTPN22"/ C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients /"JIA"/ was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the /"PTPN22"/ C1858T SNP with /"JIA"/ (p=0.66). No correlation was found between the presence of this /"PTPN22"/ SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with /"JIA"/ in a Hungarian population. However, C1858T polymorphism of /"PTPN22"/, another candidate gene of autoimmunity seems to be independent of /"JIA"/ in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to /"PTPN22"/ seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in /"JIA"/. | [
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19210888 | Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA. | Role of /"HLA-DRB1"/ and PTPN22 genes in susceptibility to /"juvenile idiopathic arthritis"/ in Hungarian patients. | OBJECTIVE: /"Juvenile idiopathic arthritis"/ (/"JIA"/) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human /"leukocyte antigen (HLA) DRB1"/ and protein tyrosine phosphatase N22 (PTPN22) with /"JIA"/ in Hungarian patients. METHODS: A case-control study including 150 /"Hungarian JIA"/ patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for /"HLA-DRB1"/ and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients /"JIA"/ was associated with /"HLA-DRB1"/*01, /"DRB1"/*08, /"DRB1"/*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with /"JIA"/ (p=0.66). No correlation was found between the presence of this PTPN22 SNP and /"HLA-DRB1"/ alleles. CONCLUSIONS: Our results confirm that certain /"HLA-DRB1"/ alleles reported previously as susceptibility factors are strongly associated with /"JIA"/ in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of /"JIA"/ in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of /"HLA-DRB1"/ in /"JIA"/. | [
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19210888 | Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA. | Role of /"HLA-DRB1"/ and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for /"autoimmunity"/, human /"leukocyte antigen (HLA) DRB1"/ and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for /"HLA-DRB1"/ and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with /"HLA-DRB1"/*01, /"DRB1"/*08, /"DRB1"/*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and /"HLA-DRB1"/ alleles. CONCLUSIONS: Our results confirm that certain /"HLA-DRB1"/ alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of /"autoimmunity"/ seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of /"HLA-DRB1"/ in JIA. | [
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19210888 | Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA. | Role of /"HLA-DRB1"/ and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. | OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for /"autoimmunity"/, human /"leukocyte antigen (HLA) DRB1"/ and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for /"HLA-DRB1"/ and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with /"HLA-DRB1"/*01, /"DRB1"/*08, /"DRB1"/*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and /"HLA-DRB1"/ alleles. CONCLUSIONS: Our results confirm that certain /"HLA-DRB1"/ alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of /"autoimmunity"/ seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of /"HLA-DRB1"/ in JIA. | [
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19220408 | Upregulated TWIK-related acid-sensitive K+ channel-2 in neurons and perivascular astrocytes in the hippocampus of experimental temporal lobe epilepsy. | PURPOSE: To identify the modulation of Tandem of P-domains in a weak inwardly rectifying K(+) channel (TWIK)-related acid-sensitive K(+) (TASK)-2 channel expressions in epilepsy, we conducted a comparative analysis of TASK-2 channel immunoreactivity in the hippocampus of a pilocarpine-induced rat epilepsy model. METHODS: We performed and immunohistochemical study for TASK-2 and double immunofluorescent staining for TASK-2 and glial fibrillary acidic protein (GFAP) in the rat hippocampus of pilocarpine-induced epilepsy models. RESULTS: In control animals, TASK-2 immunoreactivity was strongly detected in CA1-3 pyramidal layers and dentate granule cell layer. After status epilepticus (SE), TASK-2 immunoreactivity was increased in dentate granule cell layer and CA3 pyramidal cell layer, whereas its immunoreactivity was reduced in CA1 pyramidal cell layer. In addition, TASK-2 immunoreactivity is gradually increased in perivascular regions following SE. Double immunofluorescent study revealed that the enhancement of TASK-2 immunoreactivity in perivascular regions is caused by increase in the number of TASK-2 immunoreactive endfeet of perivascular astrocytes. DISCUSSION: Our findings suggest that elevated TASK-2 immunoreactivity in neurons may contribute to rapid adaptive responses (presumably for extracellular alkalinization), which result in hyperpolarization and regulate seizure activity. In contrast, upregulated TASK-2 immunoreactivity in perivascular regions may be involved in abnormalities of blood flow regulation or brain-blood barrier impairment. These changes may contribute to acquisition of the properties of the epileptic hippocampus. | Upregulated TWIK-related acid-sensitive K+ channel-2 in neurons and perivascular astrocytes in the hippocampus of experimental temporal lobe epilepsy. | PURPOSE: To identify the modulation of Tandem of P-domains in a weak inwardly rectifying K(+) channel (TWIK)-related acid-sensitive K(+) (TASK)-2 channel expressions in epilepsy, we conducted a comparative analysis of /"TASK-2"/ channel immunoreactivity in the hippocampus of a pilocarpine-induced rat epilepsy model. METHODS: We performed and immunohistochemical study for /"TASK-2"/ and double immunofluorescent staining for /"TASK-2"/ and glial fibrillary acidic protein (GFAP) in the rat hippocampus of pilocarpine-induced epilepsy models. RESULTS: In control animals, /"TASK-2"/ immunoreactivity was strongly detected in CA1-3 pyramidal layers and dentate granule cell layer. After /"status epilepticus"/ (/"SE"/), /"TASK-2"/ immunoreactivity was increased in dentate granule cell layer and CA3 pyramidal cell layer, whereas its immunoreactivity was reduced in CA1 pyramidal cell layer. In addition, /"TASK-2"/ immunoreactivity is gradually increased in perivascular regions following /"SE"/. Double immunofluorescent study revealed that the enhancement of /"TASK-2"/ immunoreactivity in perivascular regions is caused by increase in the number of /"TASK-2"/ immunoreactive endfeet of perivascular astrocytes. DISCUSSION: Our findings suggest that elevated /"TASK-2"/ immunoreactivity in neurons may contribute to rapid adaptive responses (presumably for extracellular alkalinization), which result in hyperpolarization and regulate seizure activity. In contrast, upregulated /"TASK-2"/ immunoreactivity in perivascular regions may be involved in abnormalities of blood flow regulation or brain-blood barrier impairment. These changes may contribute to acquisition of the properties of the epileptic hippocampus. | [
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19220408 | Upregulated TWIK-related acid-sensitive K+ channel-2 in neurons and perivascular astrocytes in the hippocampus of experimental temporal lobe epilepsy. | PURPOSE: To identify the modulation of Tandem of P-domains in a weak inwardly rectifying K(+) channel (TWIK)-related acid-sensitive K(+) (TASK)-2 channel expressions in epilepsy, we conducted a comparative analysis of TASK-2 channel immunoreactivity in the hippocampus of a pilocarpine-induced rat epilepsy model. METHODS: We performed and immunohistochemical study for TASK-2 and double immunofluorescent staining for TASK-2 and glial fibrillary acidic protein (GFAP) in the rat hippocampus of pilocarpine-induced epilepsy models. RESULTS: In control animals, TASK-2 immunoreactivity was strongly detected in CA1-3 pyramidal layers and dentate granule cell layer. After status epilepticus (SE), TASK-2 immunoreactivity was increased in dentate granule cell layer and CA3 pyramidal cell layer, whereas its immunoreactivity was reduced in CA1 pyramidal cell layer. In addition, TASK-2 immunoreactivity is gradually increased in perivascular regions following SE. Double immunofluorescent study revealed that the enhancement of TASK-2 immunoreactivity in perivascular regions is caused by increase in the number of TASK-2 immunoreactive endfeet of perivascular astrocytes. DISCUSSION: Our findings suggest that elevated TASK-2 immunoreactivity in neurons may contribute to rapid adaptive responses (presumably for extracellular alkalinization), which result in hyperpolarization and regulate seizure activity. In contrast, upregulated TASK-2 immunoreactivity in perivascular regions may be involved in abnormalities of blood flow regulation or brain-blood barrier impairment. These changes may contribute to acquisition of the properties of the epileptic hippocampus. | Upregulated TWIK-related acid-sensitive K+ channel-2 in neurons and perivascular astrocytes in the hippocampus of experimental temporal lobe epilepsy. | PURPOSE: To identify the modulation of Tandem of P-domains in a weak inwardly rectifying K(+) channel (TWIK)-related acid-sensitive K(+) (TASK)-2 channel expressions in epilepsy, we conducted a comparative analysis of /"TASK-2"/ channel immunoreactivity in the hippocampus of a pilocarpine-induced rat epilepsy model. METHODS: We performed and immunohistochemical study for /"TASK-2"/ and double immunofluorescent staining for /"TASK-2"/ and glial fibrillary acidic protein (GFAP) in the rat hippocampus of pilocarpine-induced epilepsy models. RESULTS: In control animals, /"TASK-2"/ immunoreactivity was strongly detected in CA1-3 pyramidal layers and dentate granule cell layer. After status epilepticus (SE), /"TASK-2"/ immunoreactivity was increased in dentate granule cell layer and CA3 pyramidal cell layer, whereas its immunoreactivity was reduced in CA1 pyramidal cell layer. In addition, /"TASK-2"/ immunoreactivity is gradually increased in perivascular regions following SE. Double immunofluorescent study revealed that the enhancement of /"TASK-2"/ immunoreactivity in perivascular regions is caused by increase in the number of /"TASK-2"/ immunoreactive endfeet of perivascular astrocytes. DISCUSSION: Our findings suggest that elevated /"TASK-2"/ immunoreactivity in neurons may contribute to rapid adaptive responses (presumably for extracellular alkalinization), which result in hyperpolarization and regulate /"seizure"/ activity. In contrast, upregulated /"TASK-2"/ immunoreactivity in perivascular regions may be involved in abnormalities of blood flow regulation or brain-blood barrier impairment. These changes may contribute to acquisition of the properties of the epileptic hippocampus. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic /"colorectal cancer"/ in the Czech Republic. | The Czech Republic has one of the highest incidences of /"colorectal cancer"/ (/"CRC"/) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the /"TP53"/ (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based /"CRC"/ cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with /"CRC"/ risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the /"TP53"/ gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the /"TP53"/ gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the /"TP53"/ gene may modulate /"CRC"/ risks in the population. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic /"colorectal cancer"/ in the Czech Republic. | The Czech Republic has one of the highest incidences of /"colorectal cancer"/ (/"CRC"/) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and /"CDKN2A"/ (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based /"CRC"/ cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with /"CRC"/ risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and /"CDKN2A"/ polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate /"CRC"/ risks in the population. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic /"colorectal cancer"/ in the Czech Republic. | The Czech Republic has one of the highest incidences of /"colorectal cancer"/ (/"CRC"/) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), /"CDKN1A"/ (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based /"CRC"/ cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with /"CRC"/ risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the /"CDKN1A"/ and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate /"CRC"/ risks in the population. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic /"colorectal cancer"/ in the Czech Republic. | The Czech Republic has one of the highest incidences of /"colorectal cancer"/ (/"CRC"/) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based /"CRC"/ cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with /"CRC"/ risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)/"GCG"/ and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)/"GCG"/), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)/"GCG"/ (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate /"CRC"/ risks in the population. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic /"colorectal cancer"/ in the Czech Republic. | The Czech Republic has one of the highest incidences of /"colorectal cancer"/ (/"CRC"/) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based /"CRC"/ cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with /"CRC"/ risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)/"GCG"/ and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)/"GCG"/), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)/"GCG"/ (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate /"CRC"/ risks in the population. | [
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19224585 | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. | Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. | The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the /"TP53"/ (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the /"TP53"/ gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the /"TP53"/ gene was similar in /"colon (global P<0.0001) and rectal cancers"/ (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the /"TP53"/ gene may modulate CRC risks in the population. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in /"SLE"/ susceptibility genes: STAT4 and BLK, but not /"PXK"/, are associated with /"systemic lupus erythematosus"/ in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for /"systemic lupus erythematosus"/ (/"SLE"/) between populations of European origin and two Asian populations. Using 910 /"SLE"/ patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 /"SLE"/ patients and 383 controls in Thailand, we studied association of STAT4, BLK and /"PXK"/ with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with /"SLE"/. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for /"PXK"/, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in /"SLE"/ susceptibility genes: /"STAT4"/ and BLK, but not PXK, are associated with /"systemic lupus erythematosus"/ in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for /"systemic lupus erythematosus"/ (/"SLE"/) between populations of European origin and two Asian populations. Using 910 /"SLE"/ patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 /"SLE"/ patients and 383 controls in Thailand, we studied association of /"STAT4"/, BLK and PXK with the disease. Our data confirmed association of /"STAT4"/ (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with /"SLE"/. It was showed that rs7574865 of /"STAT4"/ is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in /"STAT4"/ were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in /"SLE"/ susceptibility genes: STAT4 and /"BLK"/, but not PXK, are associated with /"systemic lupus erythematosus"/ in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for /"systemic lupus erythematosus"/ (/"SLE"/) between populations of European origin and two Asian populations. Using 910 /"SLE"/ patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 /"SLE"/ patients and 383 controls in Thailand, we studied association of STAT4, /"BLK"/ and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and /"BLK"/ (rs13277113, OR=0.77, P=1.34 x 10(-5)) with /"SLE"/. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in SLE susceptibility genes: STAT4 and /"BLK"/, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, /"BLK"/ and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and /"BLK"/ (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to /"hematologic disorders"/ and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in SLE susceptibility genes: STAT4 and /"BLK"/, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, /"BLK"/ and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and /"BLK"/ (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to /"hematologic disorders"/ and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19225526 | Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | Population differences in SLE susceptibility genes: STAT4 and BLK, but not /"PXK"/, are associated with systemic lupus erythematosus in Hong Kong Chinese. | In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and /"PXK"/ with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to /"hematologic disorders"/ and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for /"PXK"/, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. | [
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19228880 | A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer. | Although a number of studies have been conducted to address the relation between a gene deletion polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer, no definite conclusion has been reached and no clear risk pattern has yet to emerge for GSTM1. We first conducted case-control studies that included 1920 subjects using a genotyping method allowing the definition of GSTM1-null (-/-), homozygous wild-type (+/+), and heterozygous (+/-) genotypes. The results show that GSTM1(-/-) confers an increased risk for breast cancer development compared with that in GSTM1-present individuals (+/+ and +/-), which was subsequently confirmed by a meta-analysis of all of the 41 relevant studies (odds ratio: 1.10, P<0.001). Unexpectedly, we found that GSTM1(+/+) is also a risk genotype compared with GSTM1(+/-). Furthermore, we identified a functional polymorphism in the GSTM1 promoter region associated with breast cancer. The variant allele modifies DNA binding to the AP-2alpha transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low-activity allele is associated with reduced breast cancer risk. It seems that approximately 60-70% expression from one allele of GSTM1 could suffice for protection against breast cancer; null activity and overactivity of GSTM1 are both disadvantageous. These results indicate a U-shaped association of GSTM1 with breast cancer, which challenges the linear gene-dosage effect of GSTM1 that was previously proposed. We recommend that a more complicated role for GSTM1 should be considered in breast cancer risk prediction. | A functional polymorphism in the promoter region of /"GSTM1"/ implies a complex role for /"GSTM1"/ in /"breast cancer"/. | Although a number of studies have been conducted to address the relation between a gene deletion polymorphism of /"glutathione S-transferase M1"/ (/"GSTM1"/) and /"breast cancer"/, no definite conclusion has been reached and no clear risk pattern has yet to emerge for /"GSTM1"/. We first conducted case-control studies that included 1920 subjects using a genotyping method allowing the definition of /"GSTM1"/-null (-/-), homozygous wild-type (+/+), and heterozygous (+/-) genotypes. The results show that /"GSTM1"/(-/-) confers an increased risk for /"breast cancer"/ development compared with that in /"GSTM1"/-present individuals (+/+ and +/-), which was subsequently confirmed by a meta-analysis of all of the 41 relevant studies (odds ratio: 1.10, P<0.001). Unexpectedly, we found that /"GSTM1"/(+/+) is also a risk genotype compared with /"GSTM1"/(+/-). Furthermore, we identified a functional polymorphism in the /"GSTM1"/ promoter region associated with /"breast cancer"/. The variant allele modifies DNA binding to the AP-2alpha transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low-activity allele is associated with reduced /"breast cancer"/ risk. It seems that approximately 60-70% expression from one allele of /"GSTM1"/ could suffice for protection against /"breast cancer"/; null activity and overactivity of /"GSTM1"/ are both disadvantageous. These results indicate a U-shaped association of /"GSTM1"/ with /"breast cancer"/, which challenges the linear gene-dosage effect of /"GSTM1"/ that was previously proposed. We recommend that a more complicated role for /"GSTM1"/ should be considered in /"breast cancer"/ risk prediction. | [
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19228880 | A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer. | Although a number of studies have been conducted to address the relation between a gene deletion polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer, no definite conclusion has been reached and no clear risk pattern has yet to emerge for GSTM1. We first conducted case-control studies that included 1920 subjects using a genotyping method allowing the definition of GSTM1-null (-/-), homozygous wild-type (+/+), and heterozygous (+/-) genotypes. The results show that GSTM1(-/-) confers an increased risk for breast cancer development compared with that in GSTM1-present individuals (+/+ and +/-), which was subsequently confirmed by a meta-analysis of all of the 41 relevant studies (odds ratio: 1.10, P<0.001). Unexpectedly, we found that GSTM1(+/+) is also a risk genotype compared with GSTM1(+/-). Furthermore, we identified a functional polymorphism in the GSTM1 promoter region associated with breast cancer. The variant allele modifies DNA binding to the AP-2alpha transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low-activity allele is associated with reduced breast cancer risk. It seems that approximately 60-70% expression from one allele of GSTM1 could suffice for protection against breast cancer; null activity and overactivity of GSTM1 are both disadvantageous. These results indicate a U-shaped association of GSTM1 with breast cancer, which challenges the linear gene-dosage effect of GSTM1 that was previously proposed. We recommend that a more complicated role for GSTM1 should be considered in breast cancer risk prediction. | A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in /"breast cancer"/. | Although a number of studies have been conducted to address the relation between a gene deletion polymorphism of glutathione S-transferase M1 (GSTM1) and /"breast cancer"/, no definite conclusion has been reached and no clear risk pattern has yet to emerge for GSTM1. We first conducted case-control studies that included 1920 subjects using a genotyping method allowing the definition of GSTM1-null (-/-), homozygous wild-type (+/+), and heterozygous (+/-) genotypes. The results show that GSTM1(-/-) confers an increased risk for /"breast cancer"/ development compared with that in GSTM1-present individuals (+/+ and +/-), which was subsequently confirmed by a meta-analysis of all of the 41 relevant studies (odds ratio: 1.10, P<0.001). Unexpectedly, we found that GSTM1(+/+) is also a risk genotype compared with GSTM1(+/-). Furthermore, we identified a functional polymorphism in the GSTM1 promoter region associated with /"breast cancer"/. The variant allele modifies DNA binding to the /"AP-2alpha"/ transcription factor, resulting in reduced promoter activity and mRNA expression. However, this low-activity allele is associated with reduced /"breast cancer"/ risk. It seems that approximately 60-70% expression from one allele of GSTM1 could suffice for protection against /"breast cancer"/; null activity and overactivity of GSTM1 are both disadvantageous. These results indicate a U-shaped association of GSTM1 with /"breast cancer"/, which challenges the linear gene-dosage effect of GSTM1 that was previously proposed. We recommend that a more complicated role for GSTM1 should be considered in /"breast cancer"/ risk prediction. | [
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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in /"Alzheimer's disease"/. | OBJECTIVE: /"Alzheimer's disease"/ (/"AD"/) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in /"AD"/ has been supported. Polymorphisms within dopamine receptors DRD1, /"DRD2"/, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable /"AD"/ patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), /"DRD2"/ (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in /"AD"/ patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in /"Alzheimer's disease"/. | OBJECTIVE: /"Alzheimer's disease"/ (/"AD"/) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in /"AD"/ has been supported. Polymorphisms within dopamine receptors /"DRD1"/, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable /"AD"/ patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the /"DRD1"/ (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in /"AD"/ patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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19235789 | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in Alzheimer's disease. | OBJECTIVE: Alzheimer's disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in AD has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and DRD4 have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable AD patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and DRD4 (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between DRD4 with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of DRD4 in the development of depression in AD patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | Investigation of dopamine receptors in susceptibility to behavioural and psychological symptoms in /"Alzheimer's disease"/. | OBJECTIVE: /"Alzheimer's disease"/ (/"AD"/) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to the development of BPSD in /"AD"/ has been supported. Polymorphisms within dopamine receptors DRD1, DRD2, DRD3 and /"DRD4"/ have previously been investigated in a few interesting studies that are reviewed here and extended using our patient cohort. METHODS: Our large cohort of 395 probable /"AD"/ patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period, or not. These measures were related to the DRD1 (A-48G), DRD2 (ser311cys; C-ins/del), DRD3 (ser9gly) and /"DRD4"/ (VNTR) genotype and allele frequencies. RESULTS: Associations were revealed between DRD3 and elation, and between /"DRD4"/ with agitation/aggression and with depression; however, these findings do not remain significant after correction for multiple testing. No associations were found with the other genetic variants and these symptoms and no associations were observed between any of the polymorphic variants examined and delusions, hallucinations, psychosis and aberrant motor behaviour. CONCLUSION: Our data, in combination with a review of the literature, reveal a potential role for the VNTR variant of /"DRD4"/ in the development of depression in /"AD"/ patients. The findings presented here need to be replicated in large, well characterised longitudinal cohorts. | [
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