Associations of common genetic variants on IL-17 genes and carotid intima-media thickness

Abstract

Aim: Atherosclerosis is a chronic inflammatory process of the arterial wall and carotid intima-media thickness (cIMT) is regarded as its early marker. Several members of the IL-17 family are involved in pro-inflammatory functions. The specific aim of the study was to explore the relationships of common genetic variants on IL-17 genes with cIMT thickening. Methods: In the discovery stage, 146 SNPs on 11 IL-17 genes were screened for their relationships with cIMT by a case-control study that enrolled 284 and 464 subjects who had thicker and normal cIMT, respectively. Findings were replicated by an independent case-control study that enrolled 282 subjects who had thicker cIMT and 282 age-sex-matched subjects who had normal cIMT. Results: Among 134 eligible SNPs in the discovery study, only IL-17RC rs279545 was significantly correlated with cIMT (p =6.9×10 －5 ). The rs279545 and 2 nearby linked SNPs rs55847610 and rs3846167 were included in the validation study. We found that the rs279545 ＊ G, rs55847610 ＊ G, and rs3846167 ＊ C were correlated with significantly higher likelihoods of having thicker cIMT. The corresponding multivariate-adjusted ORs were 1.462 (95% CI: 1.055–2.027), 1.481 (95% CI: 1.090–2.013), and 1.589 (95% CI: 1.147–2.200), respectively. Analyses of rs279545-rs55847610 haplotypes showed that the multivariate-adjusted OR for A-A haplotype was significantly decreased (OR=0.665, 95% CI: 0.487–0.908) and for G-G haplotype was significantly increased (OR=1.539, 95% CI: 1.097–2.161). Conclusions: We first correlated cIMT, a preclinical clinical cardiovascular marker, with IL-17RC, the key molecule in the IL-17 signaling pathway. Our results indicated that IL-17RC may play critical role in the development of atherosclerotic diseases.