SIRT1 functional polymorphisms (rs12778366, rs3758391) as genetic biomarkers of susceptibility to type 2 diabetes mellitus in Iranians: a case-control study and computational analysis

Abstract

Genetic background is an important risk factor for type 2 diabetes mellitus (T2DM). We designed this study to examine the role of rs12778366 and rs3758391, two functional SIRT1 gene polymorphisms, on the risk of T2DM in an Iranian population. In this case-control study, a total of 813 subjects were enrolled. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple computational analyses were also performed to examine the potential effects of the studied variants. We found a significant association between rs12778366 polymorphism and an enhanced risk of T2DM under allelic C vs. T (OR = 1.50), codominant TC vs.TT (OR = 1.86), dominant CC + TC vs. TT (OR = 1.65), and over-dominant TC vs. CC + TT (OR = 1.80) genetic models. In contrast, codominant CT vs. CC (OR = 0.54) and dominant CT + TT vs. CC (OR = 0.68) models of rs3758391 polymorphism were correlated with decreased risk of T2DM. Compared to the TC haplotype, we have found that the CC combination significantly enhanced the risk of T2DM by 1.86-fold. Computational analyses indicated that the C allele of rs12778366 might disrupt the binding site of the CEBP transcription factor. SIRT1 rs12778366 and rs3758391 polymorphisms might be associated with T2DM susceptibility in our population. Replications in different races with larger sample sizes are necessary to yield more accurate results.