Genetic association of pro-inflammatory cytokine gene polymorphisms with coronary artery disease (CAD) in a North Indian population

Background: Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-alpha - 308 (G/A), TNF-beta + 252 (A/G), IL-6 - 174 (G/C) and IL-6 - 597 (G/A), and IFN-gamma + 874 (T/A) with coronary artery disease (CAD) among north Indian patients. Materials and methods: 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-alpha - 308 (G/A) (rs1800797), TNF-beta + 252 (A/G) (rs909253), IL-6 - 174 (G/C) (rs1800795), IL6 - 597 (G/A) (rs1800797), and IFN-gamma + 874 (T/A) (rs2430561) SNPs were genotyped by TaqMan (R) SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p <= 0.05 was considered significant. Results: Significant risk association with CAD was found for TNF-alpha - 308 (G/A) A allele (OR = 5.6, CI 1.8-17.4, p = 0.001) and TNF-beta + 252 (A/G) G allele (OR = 3.4, CI = 1.9-6.0, p < 0.001). However, no statistical significance was found for IL-6 - 174 (G/C) or IL6 - 597 (G/A), with CAD. TNF-alpha - 308 (G/A), and TNF-beta + 252 (A/G) haplotype GG AG increased CAD risk significantly (GG haplotype, adjusted OR = 2.6, CI 1.4-5.0, p = 0.003 and AG haplotype OR = 8.5, CI 2.2-33.35, p = 0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. Discussion: The present study found significant risk association for TNF-alpha - 308 (G/A), and TNF-beta + 252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population.