Associations of EDNRA and EDN1 polymorphisms with carotid intima media thickness through interactions with gender, regular exercise, and obesity in subjects in Taiwan: Taichung Community Health Study (TCHS).

Tsai-Chung Li,Li-Na Liao,Fang-Yang Wu,Chih-Hsueh Lin,Chia-Ing Li,Cheng-Chieh Lin,Wen-Yuan Lin,Chiu-Shong Liu,Jen-Hao Hsiao,Chuan-Wei Yang,Chih-Yi Hsiao

doi:10.7603/s40681-015-0008-7

Abstract

The aim of this study was to evaluate the interacted association between EDNRA and EDN1 polymorphisms and gender, regular exercise, and obesity status on carotid intima media thickness (IMT) in community- dwelling subjects of the Taichung Community Health Study. Five single-nucleotide polymorphisms (SNPs rs1395821, rs1878406, rs5333, rs1800541, and rs5370) of the EDNRA and EDN1 gene were examined in 480 participants from 160 families. The IMT protocol involves scanning the common carotid arteries (CCAs), the carotid bifurcations (bulb), and the origins (first 1 cm) of the internal carotid arteries (ICAs). Generalized linear models with a generalized estimating equation were employed to consider the dependence among family members. After multivariate adjustment, the effects of interactions between EDNRA and EDN1 gene with gender, obesity, and exercise were observed. For gene-gender interaction on CCA IMT, the adjusted mean for men carrying the GA/GG genotype of EDNRASNP rs1878406 was 1.18 times higher than that for men carrying the AA genotype (95% CI: 1.01, 1.37). As for bulb and ICA IMT, the adjusted mean values for women carrying the AC/AA genotype of EDN1 rs5370 was lower than those carrying the CC genotype: 0.89, [0.82, 0.98]; and 0.90 [0.83, 0.99], respectively. We did observe significant effects of EDNRA SNPs rs1395821 and rs5333 in individuals who regularly exercised. A significantly lower adjusted mean in CCA IMT for non-obese individuals carrying EDNRA SNP rs5333 was observed (0.92 [0.86, 0.99]) compared with non-obese individuals carrying the AA genotype. This study first reported significant interactions of EDNRA and EDN1 polymorphisms with gender, regular exercise, and obesity on carotid IMT in Han Chinese participants.

Highlights

Cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, and peripheral arterial disease, is responsible for a lot of morbidity and premature mortality
We examined the evidence for gene-gender, gene-exercise, and geneobesity interaction between the two single-nucleotide polymorphism (SNP) in the EDN1 gene and three SNPs in the EDNRA gene in relation to carotid intima-media thickness (IMT) in Han Chinese subjects of Taiwan
Regular exercise, and obesity significantly interacted with SNPs in the EDNRA gene, and gender interacted with SNPs in the EDN1 gene to influence carotid IMTs in the Han Chinese participants of the Taichung Community Health Study (TCHS)

Summary

Introduction

Cardiovascular disease (CVD), including coronary heart disease (CHD), stroke, and peripheral arterial disease, is responsible for a lot of morbidity and premature mortality. The pathogenesis of CVD appears to be multi-factorial. Genetics and environments are two major determinants that result in the development of metabolic syndrome, a cluster of CVD risk factors. These CVD risk factors include high blood pressure, high (pro)-insulin concentrations, excess body weight with central obesity, an altered lipid profile (dyslipidaemia), and inflammation which increases the likelihood of developing atherosclerosis. Carotid intima-media thickness (IMT) is a quantitative measure of subclinical atherosclerosis [1]. # Equal contribution as the first author During the progression of Taiwan. # Equal contribution as the first author

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