Pro-inflammatory cytokine gene polymorphisms and threat for coronary heart disease in a North Indian Agrawal population

The association of IFN-γ (+ 874 A/T; rs2430561), TNF-α (− 308 G/A; rs1800629) and TNF-β (+ 252 A/G; rs909253) with Coronary Heart Disease (CHD) has not been rigorously tested in Indian population. In the present study we sought to examine the role of these cytokines in the causation of CHD and their association with conventional CHD risk factors. A total of 138 case and 187 unrelated healthy controls aged 35 to 80 years, matched on ethnicity and geography were collected from North Indian Agrawal population. Single nucleotide polymorphisms at the promoter TNF-α − 308 G/A and the intronic IFN-γ + 874 A/T were analyzed by allele-specific PCR, and the intronic TNF-β + 252 A/G was analyzed by RFLP. Of the three selected polymorphisms, genotypic distribution of IFN-γ + 874 A/T and TNF-β + 252 A/G polymorphisms was significantly different between patients and controls in the present study. OR revealed statistically significant risk for CHD with respect to IFN-γ + 874 T allele, whereas OR for TNF-β + 252 A/G showed three fold risk in homozygous condition though not significant. No such trend could be observed for TNF-α − 308 G/A polymorphism. Multivariate logistic regression after adjusting for all the confounders showed significant risk for CHD with the genotypes and genotypic combinations of all the three markers (albeit not significant with TNF-α). Increased risk for CHD was likely to be associated with interaction of IFN-γ with diastolic hypertension, TNF-α with diabetes and BMI, and TNF-β with serum triglyceride and very low density lipoprotein (VLDL) levels. The results suggest that these selected cytokine polymorphisms could possibly serve as potential bio-markers for CHD in conjunction with specific conventional risk factors.

► Examined association of IFN-γ 874 A/T, TNF-α 308 G/A, and TNF-β 252 A/G with CHD
► IFN-γ 874 A/T and TNF-β 252 A/G were associated with CHD and other risk factors.
► TNF-α 308 G/A was not associated with CHD but associated with various risk factors.
► Absence of AA in cases indicates lethality of TNF-α 308 G/A through risk factors.
► Selected cytokine polymorphisms could serve as potential bio-markers for CHD.