Functional Polymorphisms in Interleukin-23 Receptor and Susceptibility to Coronary Artery Disease

Abstract

As a key element in the T-helper 17 (Th17) cell-mediated inflammatory process, interleukin-23 receptor (IL-23R) may play a crucial role in the pathogenesis of atherosclerosis. Single nucleotide polymorphisms (SNPs) in IL-23R have been studied in several diseases. However, its association with coronary artery disease (CAD) remains unclear. This study examined whether genetic polymorphisms in IL-23R were associated with susceptibility to CAD. Two IL-23R SNPs, rs1884444 and rs6682925, were genotyped in 462 CAD patients and 486 healthy controls. Data showed that percentages of rs6682925TC and CC genotypes were significantly higher in patients than in controls (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.04-1.79, p = 0.022; OR = 2.35, 95% CI: 1.52-3.43, p < 0.001, respectively). Frequency of the rs1884444 polymorphism did not reveal any significant differences between patients and healthy donors. Further analyses demonstrated a significantly increased number of rs6682925CC genotype in patients with hypertension. Moreover, we investigated the effect of IL-23R polymorphisms on gene expression by assessing mRNA level of IL-23R in peripheral blood mononucleated cells (PBMCs). Results showed that subjects carrying rs6682925TC and CC genotypes had significantly increased mRNA level of IL-23R in PBMCs than those with TT genotype. These data suggest that IL-23R rs6682925T/C polymorphism may act as a risk factor of CAD.

IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

“…IL-23 has been shown to participate in many inflammatory diseases, such as inflammatory bowel disease, psoriasis and coronary heart disease [6,7,8]. There are emerging evidence suggests that HMGB1-TLR4-IL-23/IL-17 axis plays a critical role in initiating and enhancing the inflammatory responses and ROS production during myocardial I/R [9,10,11].…”

Plasmatic MicroRNA Signatures in Elderly People with Stable and Unstable Angina

“…23,24) Zhang, et al found IL-23R rs6682925T/C polymorphism acted as a risk factor in process of atherosclerosis. 25) Mir-3162-3p may be an important factor involved in the formation of atherosclerosis by modulating IL-23R.…”

IL-6-174G/C and IL-6-572C/G polymorphisms are associated with increased risk of coronary artery disease

“…Many epidemiologic studies have observed that polymorphisms in the genes encoding interleukin-1 receptor antagonist, such as , are associated with the development of CAD (Zhang et al, 2011;Huang et al, 2013;Opstad et al, 2011Opstad et al, , 2013Galimudi et al, 2014;He et al, 2014;Zhang et al, 2014).…”

“…One animal experimental study has shown that several cytokines play a key role in the development of CAD (Kleemann et al, 2008). Several previous epidemiology studies have shown that polymorphisms in several cytokines, including interleukin-6 (IL-6), , are involved in the pathogenesis of CAD (Zhang et al, 2011;Huang et al, 2013;Opstad et al, 2011Opstad et al, , 2013Galimudi et al, 2014;He et al, 2014;Zhang et al, 2014). However, the results of these studies are inconsistent.…”