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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-α − 308 (G/A), TNF-β + 252 (A/G), IL-6 − 174 (G/C) and IL-6 − 597 (G/A), and IFN-ɣ + 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-α − 308 (G/A) (rs1800797), TNF-β + 252 (A/G) (rs909253), IL-6 − 174 (G/C) (rs1800795), IL6 − 597 (G/A) (rs1800797), and IFN-ɣ + 874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®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-α − 308 (G/A) “A” allele (OR = 5.6, CI 1.8–17.4, p = 0.001) and TNF-β + 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-α − 308 (G/A), and TNF-β + 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-α − 308 (G/A), and TNF-β + 252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population. [ABSTRACT FROM AUTHOR]