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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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC4248252 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Functional polymorphisms in interleukin-23 receptor and susceptibility to coronary artery disease.

Zhang Meiyan M Cai Zhen-Rong ZR Zhang Bili B Cai Xinmeng X Li Wei W Guo Zhifu Z Ma Lan L

DNA and cell biology 20141201 12

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 genotype ...[more]

PMID: 25192515

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Project description:BackgroundStudies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility.MethodsPubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases.ResultsThirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process.ConclusionsOur analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism.LimitationsFirstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

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Functional polymorphisms in interleukin-23 receptor and susceptibility to coronary artery disease.

Publications

Functional polymorphisms in interleukin-23 receptor and susceptibility to coronary artery disease.

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