Background: Tumor necrosis factor-alpha (TNF-α) is a cytokine of proinflmmatory that elicits a polyvalent initial response of inflammatory cells in coronary atherosclerosis. Polymorphism and susceptibility to atherosclerosis may be related to the TNF-α gene promoter. The aim of this study was to investigate single nucleotide polymorphisms of the TNF-α gene promoter at two sites in patients with atherosclerosis referred to the Fatemeh al-Zahra Hospital, Sari City.
Methods: This study was a case control study which involved 120 patients (>50% stenosis) and 120 healthy individuals (<10% stenosis). Genomic DNA was extracted with the phenol-chloroform method from white blood cells. Genotypes and TNF-α gene polymorphisms were analyzed using RFLP-PCR. Genotype frequency analysis, Hardy-Weinberg equilibrium test, and chi-square analysis have been conducted using SPSS software, version 22.
Results: Genotype frequencies of GA, GG, and AA at position –308 of the TNF-α gene promoter in patients were 12.5%, 75%, and 12.5%, respectively. The respective values in healthy subjects were 7.5%, 21.7%, and 70.8%. Allele A to G polymorphism increased the risk of disease by 12.716%. The genotype frequencies of the AC, CC, and AA at position –863 of the TNF-α gene promoter in patients were 3.3%, 69.2%, and 27.5%, respectively. The respective values in healthy individuals were 2.5%, 11.7%, and 85.8%. Allele A to C polymorphism increased the risk of the disease by 16.373%. The difference in the risk of atherosclerosis was significant (P < 0.05).
Conclusion: Mutations in TNF-α gene promoter could increase susceptibility to atherosclerosis. Determination of the genotypes of the individuals in these regions can help identify patients at risk for this disease.