Polymorphisms in PPARγ (Pro12Ala, C1431T), IRS1 (G972R), IRS2 (G1057D) and Coronary artery disease

Abstract

Defect in insulin receptors or insulin signaling pathway is a hallmark of T2DM as it directly affects the endothelium. Coronary artery disease (CAD) being a comorbidity of T2DM, polymorphisms in genes of the insulin signaling pathway may affect an individual’s susceptibility to CAD. The objective of present study was to assess the association of CAD with polymorphisms in three genes of insulin signalling pathway; IRS1(G972R), IRS2 (G1057D) and PPARγ (Pro12Ala, C1431T). Blood samples were collected from 416 subjects of Punjabi origin; 200 CAD patients and 216 normal healthy controls matched for age and sex. For G972R polymorphism, Arg972 (A) allele carriers (GA+AA) had increased risk of CAD (OR: 1.92, CI: 1.13–3.29, P = 0.01) in overall population and in individuals with low BMI, HDL-C, high WHR, waist circumference, normal range of cholesterol and triglycerides. D allele of G1057D polymorphism was associated with increased risk of CAD (OR: 1.44, CI-1.08–1.92, P = 0.01) in overall population as well as in individuals with high BMI, WC, WHR and normal range of triglycerides and cholesterol. For PPARγ variants (Pro12Ala,C1431T), no statistical significant association was observed in the allelic and genotypic frequencies of cases and controls but TT genotype (C1431T) and G allele ( Pro12Ala) conferred protection against CAD in individuals with high cholesterol and normal HDL-C respectively. Statistically significant difference in the different genotypic combinations of IRS1 (G972R) with IRS2 (G1057D) and PPARγ (C1431T) confirmed their role in susceptibility to CAD in Punjabi population from North-west India.