Background: Variants of certain haemostatic genes(such as that encoding factor V Leiden) are involved in the development of venous thrombosis, but studies of such variants in coronary disease have reported apparently ...Background: Variants of certain haemostatic genes(such as that encoding factor V Leiden) are involved in the development of venous thrombosis, but studies of such variants in coronary disease have reported apparently conflicting results. We did meta-analyses on seven such haemostatic genetic variants for which the available evidence on each comprises at least 5000 coronary disease cases and at least 5000 controls. Methods: Meta-analyses were done of 191 studies in relation to factor V G1691A(ie, factor V Leiden), factor VII G10976A, prothrombin G20210A, plasminogen activator inhibitor-1(PAI-1) [-675] 4G/5G, and three platelet glycoprotein(GP)receptor variants(GPIa C807T, GPIbα T[-5]C,GPIIIa C1565T), involving a total of 66 155 coronary disease cases and 91 307 controls. We explored potential sources of heterogeneity. Findings: In a combined analysis of all studies, the per-allele relative risks(RR) for coronary disease of factor V 1691A and of prothrombin 20210A were 1.17(95% CI 1.08-1.28) and 1.31(1.12-1.52), respectively. Combined analyses of studies of the PAI-1 [-675] 4G variant yielded a per-allele relative risk for coronary disease of 1.06(1.02-1.10), but there was an indication of publication bias in these studies. Combined analyses of the factor VII 10976A, GPIa 807T, GPIbα [-5]C, and GPIIIa 1565T variants showed no significant overall associations with coronary disease, yielding per-allele RRs of 0.97(0.91-1.04), 1.02(0.97-1.08), 1.05(0.96-1.13), and 1.03(0.98-1.07) , respectively. Interpretation: The 1691A variant of the factor V gene and the 20210A variant of the prothrombin gene, both of which increase circulating thrombin generation, might each be moderately associated with the risk of coronary disease. Further studies are merited to assess these associations in greater detail(including any gene-gene and gene-environment interactions) and to determine any implications with regard to potential therapies designed to reverse patients prothrombotic phenotype, such as selective plasma factor V or factor Xa inhibition.展开更多
Aim:To determine whether four potential genetic factors(polymorphisms in genes for alpha-adducin,beta-adducin,the G-protein beta-3 subunit and nitric oxide synthase)are important for the development of essential hyper...Aim:To determine whether four potential genetic factors(polymorphisms in genes for alpha-adducin,beta-adducin,the G-protein beta-3 subunit and nitric oxide synthase)are important for the development of essential hypertension(EH)in Slovenian children and young adults with EH.Methods:Both a nuclear families approach and case-control study have been performed.Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families(an affected child,both parents)and in 200 control patients.Results:Using the transmission disequilibrium test,no statistically significant differences were found between the frequencies of transmitted and non-transmitted alleles in nuclear families for all four investigated polymorphisms.In addition,the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients.The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations.Conclusion:We found no association between the investigated gene variants and EH,so we conclude that they do not confer a significantly increased risk of the development of EH in the Slovenian population of hypertensive children.展开更多
Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample wa...Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6% . This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2% .展开更多
文摘Background: Variants of certain haemostatic genes(such as that encoding factor V Leiden) are involved in the development of venous thrombosis, but studies of such variants in coronary disease have reported apparently conflicting results. We did meta-analyses on seven such haemostatic genetic variants for which the available evidence on each comprises at least 5000 coronary disease cases and at least 5000 controls. Methods: Meta-analyses were done of 191 studies in relation to factor V G1691A(ie, factor V Leiden), factor VII G10976A, prothrombin G20210A, plasminogen activator inhibitor-1(PAI-1) [-675] 4G/5G, and three platelet glycoprotein(GP)receptor variants(GPIa C807T, GPIbα T[-5]C,GPIIIa C1565T), involving a total of 66 155 coronary disease cases and 91 307 controls. We explored potential sources of heterogeneity. Findings: In a combined analysis of all studies, the per-allele relative risks(RR) for coronary disease of factor V 1691A and of prothrombin 20210A were 1.17(95% CI 1.08-1.28) and 1.31(1.12-1.52), respectively. Combined analyses of studies of the PAI-1 [-675] 4G variant yielded a per-allele relative risk for coronary disease of 1.06(1.02-1.10), but there was an indication of publication bias in these studies. Combined analyses of the factor VII 10976A, GPIa 807T, GPIbα [-5]C, and GPIIIa 1565T variants showed no significant overall associations with coronary disease, yielding per-allele RRs of 0.97(0.91-1.04), 1.02(0.97-1.08), 1.05(0.96-1.13), and 1.03(0.98-1.07) , respectively. Interpretation: The 1691A variant of the factor V gene and the 20210A variant of the prothrombin gene, both of which increase circulating thrombin generation, might each be moderately associated with the risk of coronary disease. Further studies are merited to assess these associations in greater detail(including any gene-gene and gene-environment interactions) and to determine any implications with regard to potential therapies designed to reverse patients prothrombotic phenotype, such as selective plasma factor V or factor Xa inhibition.
文摘Aim:To determine whether four potential genetic factors(polymorphisms in genes for alpha-adducin,beta-adducin,the G-protein beta-3 subunit and nitric oxide synthase)are important for the development of essential hypertension(EH)in Slovenian children and young adults with EH.Methods:Both a nuclear families approach and case-control study have been performed.Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families(an affected child,both parents)and in 200 control patients.Results:Using the transmission disequilibrium test,no statistically significant differences were found between the frequencies of transmitted and non-transmitted alleles in nuclear families for all four investigated polymorphisms.In addition,the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients.The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations.Conclusion:We found no association between the investigated gene variants and EH,so we conclude that they do not confer a significantly increased risk of the development of EH in the Slovenian population of hypertensive children.
文摘Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6% . This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2% .
