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Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population.

ABSTRACT: Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02-2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01-2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05-2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03-1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

SUBMITTER: Liang LL

PROVIDER: S-EPMC6205642 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population.

Liang Li-Li LL Chen Lin L Zhou Meng-Yuan MY Cai Meng-Yun MY Cheng Jie J Chen Yi Y You Si-Kun SK Chen Lin-Bin LB Tang Zi-Bin ZB Yang Xi-Li XL Chen Can C Liu Xinguang X Xiong Xing-Dong XD

Bioscience reports 20181017 5

Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within ...[more]

PMID: 29654172

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Project description:Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.

Dataset Information

Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population.

Publications

Genetic susceptibility of five tagSNPs in the endothelin-1 (<i>EDN1</i>) gene to coronary artery disease in a Chinese Han population.

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