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The rs3737964 single-nucleotide polymorphism of the chloride channel-6 gene as a risk factor for coronary heart disease.

ABSTRACT: The present study investigates the association of single-nucleotide polymorphisms (SNPs) on the chloride channel-6 (CLC-6) gene with coronary heart disease (CHD) in China. We carried out a large case-control study among 1193 CHD patients and 1200 unrelated healthy control subjects. Information on the participants' health status was collected through the modified Inter-heart questionnaire. Genomic DNA from peripheral blood samples was analyzed for the genotypes of rs3737964 and rs3737965 SNPs on the CLC-6 gene using Taqman probe-based quantitative real-time PCR (qPCR). We compared the collected data between the case group and the control group by chi-square test and t/nonparametric test. Furthermore, we performed logistic regression to evaluate factors associated with CHD. The frequency of TT genotypes in rs3737964 was significantly higher in CHD patients compared to the control group, with an odds ratio (OR) of 2.32 (95% confidence interval, CI: 1.17-4.06, P = 0.016). The association of CHD with TT genotype was even stronger in smoking population after adjusting for confounders (OR = 3.19, 95% CI: 1.04-9.79, P = 0.043). Multivariate logistic regression showed the CHD risk associated with TT genotype in rs3737964 was particularly among population who were more than 60 years old, smoking, and male (P = 0.023, 0.008 and 0.043, respectively). The present study has revealed that rs3737964 SNP of CLC-6 was associated with CHD. In particular, subjects with TT genotype who were 60-plus years old, with smoking habit or were male were more susceptible to CHD.

SUBMITTER: Zhang L

PROVIDER: S-EPMC4694129 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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The rs3737964 single-nucleotide polymorphism of the chloride channel-6 gene as a risk factor for coronary heart disease.

Zhang Li L Zhang Tao T Xiang Zhengkai Z Lu Shengqiang S

Molecular genetics & genomic medicine 20150714 6

The present study investigates the association of single-nucleotide polymorphisms (SNPs) on the chloride channel-6 (CLC-6) gene with coronary heart disease (CHD) in China. We carried out a large case-control study among 1193 CHD patients and 1200 unrelated healthy control subjects. Information on the participants' health status was collected through the modified Inter-heart questionnaire. Genomic DNA from peripheral blood samples was analyzed for the genotypes of rs3737964 and rs3737965 SNPs on ...[more]

PMID: 26740945

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Project description:Ischemic heart disease (IHD) has a genetic predisposition and a number of cardiovascular risk factors are known to be affected by genetic factors. Development of metabolic syndrome and insulin resistance, strongly influenced by lifestyle and environmental factors, frequently occur in subjects with a genetic susceptibility. The definition of genetic factors influencing disease susceptibility would allow to identify individuals at higher risk and thus needing to be closely monitored.To this end, we focused on a complex of soluble-N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), playing an important role in metabolic syndrome and insulin resistance, involved in endothelial dysfunction and heart disease. We assessed if genetic variants of the SNARE genes are associated with IHD.SNAP25 rs363050, Stx-1A rs4717806, rs2293489, and VAMP2 26bp ins/del genetic polymorphisms were analyzed in a cohort of 100 participants who underwent heart surgery; 56 of them were affected by IHD, while 44 were not. A statistical association of plasma glycemia and insulin resistance, calculated as Triglyceride glucose (TyG) index, was observed in IHD (P < .001 and P = .03, respectively) after binomial logistic stepwise regression analysis, adjusted by age, gender, diabetes positivity, waist circumference, and cholesterol plasma level. Among genetic polymorphisms, rs4717806(A) and rs2293489(T), as well as the rs4717806 - rs2293489 (A-T) haplotype were associated with higher risk for IHD (Pc = .02; Pc = .02; P = .04, respectively). Finally, a statistical association of rs4717806(AA) genotype with higher TyG index in IHD patients (P = .03) was highlighted by multiple regression analysis considering log-transformed biochemical parameters as dependent variable and presence of coronary artery disease, age, gender, waist circumference, presence of diabetes as predictors. These results point to a role of the Stx-1A rs4717806 SNP in IHD, possibly due to its influence on Stx-1A expression and, as a consequence, on insulin secretion and glucose metabolism.

Dataset Information

The rs3737964 single-nucleotide polymorphism of the chloride channel-6 gene as a risk factor for coronary heart disease.

Publications

The rs3737964 single-nucleotide polymorphism of the chloride channel-6 gene as a risk factor for coronary heart disease.

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