Evaluation of Relationship between Single-nucleotide Polymorphism in TNF-gene Promoter and Susceptibility to Atherosclerosis in Fatemeh Zahra Hospital

Introduction: Tumor necrosis factor alpha is a proinflammatory cytokine that initiates a polyvalent initial response of inflammatory cells, which is facilitated by coronary atherosclerosis. Further, it appears that the polymorphism and susceptibility to atherosclerosis are related to the TNF-α gene promoter. Aim: To assay single nucleotide polymorphisms of the TNF-α gene promoter in two sites (863 and 308) in atherosclerotic patients referred to Fatemeh al-Zahra Hospital. Materials and Methods: This case-control study was conducted on 120 patients (with stenosis greater than 50%) and 120 healthy individuals (with stenosis lesser than 10%). Genomic DNA was extracted using the Phenol-chloroform procedure from their white blood cells. Genotypes of these individuals and TNF-α gene polymorphisms were analyzed by the RFLP-PCR method. Genotype frequencies, the Hardy-Weinberg equilibrium test, and chi-square analysis were conducted using the SPSS software version 22. Results: Genotype frequencies of GA, GG, and AA in position -308 of the TNF-α gene of patients were 12.5%, 75%, and 12.5%, respectively; in healthy subjects, they were 7.5%, 21.7%, and 70.8%, respectively. Allele A to G allele increased the risk of disease by 12.716%. The genotype frequencies of AC, CC, and AA in position -863 of the TNF-α gene of patients were 3.3%, 69.2%, and 27.5%, respectively; in healthy individuals, they were 2.5%, 11.7%, and 85.8%, respectively. Allele A to C allele increased the risk of disease by 16.373%. Statistical analysis revealed a significant correlation between the risk of atherosclerosis with single nucleotide polymorphisms in the TNF-α gene-863 at C A and in gene -308 at G A (P 0.05). Conclusion: According to this study, mutations in the promoter region of the TNF-α gene possibly increased susceptibility to atherosclerosis. Therefore, genotype determination of individuals in these areas can help to identify patients with high risk for cardiac disease.