Association between IRS-1 and IRS-2 gene polymorphisms and coronary artery disease susceptibility

Abstract

Objective: To investigate the association of two single nucleotide polymorphisms (SNPs, rs10205923 and rs16822633) in insulin receptor substrate-1 gene ( IRS- 1) and one SNP (rs9521509) in insulin receptor substrate-2 gene ( IRS- 2) with coronary artery disease (CAD) susceptibility among Chinese Han population in Guangdong province.

Methods: A total of 783 CAD patients and 749 healthy individuals were genotyped using SNPscanTM multiple SNP genotyping assay; the association between the three SNP loci and CAD was tested with Chi-square test and logistic regression model.

Results: There were no statistically significant differences in allelic and genotypic frequency distribution of the three polymorphic loci between the patients with CAD and the health controls (all P > 0.05). Multivariate logistic regression analysis did not reveal significant effect of SNPs of the three loci on CAD susceptibility under three genetic models (additive, dominant, and recessive), with the P values ranging from 0.406 to 0.949 after adjusting for several confounding factors (age, hypertension, diabetes, smoking history, and body mass index). Further haplotype analysis on the two SNPs (rs10205923 and rs16822633) in IRS- 1 did not find any haplotype that conferred significant effect on CAD susceptibility, with the covariate adjusted P values ranging from 0.439 to 0.941.

Conclusion: This study suggests that SNPs of IRS- 1 rs10205923, rs16822633 and IRS- 2 rs9521509 do not associate with the CAD susceptibility among Chinese Han population in Guangdong province.

Abstract

［摘 要］ 目的 探讨胰岛素受体底物-1 基因 ( IRS- 1) 单核苷酸多态性 (SNP) 位点 rs10205923, rs16822633 以及胰岛素受体底物-2 基因 ( IRS- 2) rs9521509 与广东汉族人群冠心病遗传易感性的关系。 方法 收集 2009 — 2012 年在广东医科大学附属医院、中山大学第一附属医院、茂名市人民医院等多家医院心血管内科住院诊治的冠心病病例 783 例和同期进行健康体检的健康人 749 名, 采用 SNPscan ^TM 多重 SNP 分型试剂盒进行基因型分型, 应用 χ ² 检验和多因素 logistic 回归模型检验 SNP 位点与冠心病的关联性。 结果 3 个 SNP 位点等位基因和基因型分布在病例和对照组间的差异均无统计学意义 ( P > 0.05) 。多因素 logistic 回归模型检验未发现这 3 个 SNP 位点在 3 种遗传模式 (加性、显性和隐性) 下对冠心病有显著影响, 校正混淆因素后 P 值 = 0.406～0.949。进一步对单体型分析未发现 IRS- 1 基因的 2 个 SNP 位点 (rs10205923 和 rs16822633) 构成单体型对冠心病有明显影响。校正混淆因素后 P 值 = 0.439～0.941。 结论 该研究提示 IRS- 1 和 IRS- 2 基因单核苷酸多态性与广东汉族人群冠心病无关联性。