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Abstract Background Coronary artery disease (CAD) is the most common kind of heart problem, currently became one of the leading causes of death worldwide and is predicted to persist so for the next 20 years. The global risk factors to CAD include atherosclerosis, genetic predisposition, environment and the lifestyle. This study is aimed to find out the genotypic association of PON1 (rs662) and TNF-α (rs1799964) genes with CAD among North Indian populations. A total of 330 subjects including 175 CAD cases and 155 healthy controls were enrolled in this study. Single nucleotide polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) method. χ2 and Student's t-tests were applied for the comparison of alleles and genotype frequencies in cases and controls. Logistic regression analysis was applied to calculate the 95% confidence intervals and odds ratios (OR) for assessing the association of genotype with disease. Results The PON1 gene QQ, QR, RR genotypes frequencies were 36.57%, 50.29%, 13.14% in CAD cases and 60%, 38.71%, 1.29% in controls, respectively. OR for the genotype QQ, QR, RR was 0.38, 1.6, 11.57 (P