SIRT1 gene polymorphisms associated with decreased risk of atherosclerotic coronary artery disease

Abstract

Coronary artery disease (CAD) exhibits the rules of the multifactorial hereditary. Notwithstanding, the role of genetic factors in the prevalence of CAD is estimated very high. SIRT1 plays an athero-protective role and alterations in its expression have some important consequence in the metabolism, cholesterol, and fat deposition. The aim of our study was to investigate the association between rs4746720, rs12413112, and rs1467568 polymorphisms in the SIRT1 gene and CAD in the high-risk cases. In the present retrospective case-control study, 150 healthy individuals and 150 cases diagnosed with atherosclerotic lesions were investigated. ARMS PCR was used to determine the genotypes of rs4746720 polymorphism, while tetra primer-ARMS PCR was used for genotyping of rs12413112 and rs1467568 polymorphisms. Considering rs12413112 polymorphism, the frequency of the AG heterozygote genotype was significantly lower in cases than controls (P < 0.001). Furthermore, the frequency of the A-positive (AA+AG vs. GG) genotype was significantly different between groups (P < 0.001). The frequency of the variant A allele was 0.36% in cases and 0.46% in controls (P = 0.01). Except for a borderline protective effect in the present of rs1467568AG genotype, the allele and genotype distributions of both rs1467568 and rs4746720 polymorphisms did not differ between two groups. The haplotype constructed from rs1467568A, rs12413112A, and rs4746720T alleles showed a significant protective effect on the risk of CAD (OR: 0.53; 95%CI: 0.35–0.78; P = 0.001). In conclusion, the SIRT1 gene may contribute to the pathogenesis of CAD, while further investigations were suggested to confirm our results.