Genetic association of Tumour necrosis factor alpha, Interleukin-18 and Interleukin 1 beta with the risk of coronary artery disease: A case-control study outcome from Kashmir

Abstract

Coronary artery disease (CAD) is a clinical manifestation of atherosclerosis in the arteries supplying myocardium. Inflammation is the cornerstone in the development and progression of atherosclerosis. Amongst the various biomolecules tumour necrosis factor-α (TNF-α), interleukin-18 (IL-18) and interleukin-1β (IL-1β) build an inflammatory bionetwork in developing the disease. In this study we investigated the association of TNF-α SNPs [–308G/A (rs1800629), −1031T/C (rs1799964), −863C/A (rs1800630)]; IL-18 [–137G/C (rs187238)] and IL-1β SNPs [+3954C/T (rs1143634), −31C/T (rs1143627), and −511C/T (rs16944)] with coronary artery disease risk in Kashmiri population. A total of 200 cases and 260 controls were recruited in the study. Logistic regression analysis was done to investigate the association between SNPs and CAD risk. In case of TNF-α, the −308G/A-A/A and −863A/A showed an association with disease while −1031T/C was found to have an inverse relation. The IL-18–137G/C showed no statistically significant difference between controls and cases. For IL-1β the +3954C/T and −31C/T SNP variants showed no disease association while −511T/T showed significant association. Haplotypic analysis revealed the haplotype ATCGCC and GTACCTC to be associated with CAD risk and GTCGTTT, in particular, showing a profound association. Overall, our study suggests that TNF-α and IL-1β promoter polymorphisms may act as genetic risk factors in developing the coronary artery disease.