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)

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.