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

Li-Li Liang,Meng-Yun Cai,Si-Kun You,Xinguang Liu,Can Chen,Xi-Li Yang,Lin-Bin Chen,Yi Chen,Jie Cheng,Lin Chen,Xing-Dong Xiong,Meng-Yuan Zhou,Zi-Bin Tang

doi:10.1042/bsr20171320

Li-Li Liang, Meng-Yun Cai + Show 11 more

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https://doi.org/10.1042/bsr20171320

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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.

Highlights

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in humans worldwide, despite advances in treatment and lifestyle modification
Lipid profile data demonstrated significantly higher levels of triglyceride (TG), low-density lipoprotein cholesterol (LDLC) and lower levels of high-density lipoprotein cholesterol (HDLC) in CAD patients when compared with controls
Genetic association studies have provided tremendous insight into the diversity of genetic factors contributing to the risk of CAD [20,22,28]

Summary

Introduction

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in humans worldwide, despite advances in treatment and lifestyle modification. Both genetic and environmental factors contribute to the occurrence and development of CAD, as evident by its high heritability in twin and family studies [1]. Previous studies have reported that an assessment of genetic risk burden can identify individuals at increased risk for incident CAD in population-based epidemiological cohorts [2,3,4]. Several studies have found that endothelial dysfunction was detectable in the early stage of CAD, which could c 2018 The Author(s).

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