Common Genetic Variants in SIRT1 Gene Promoter and Type 2 Diabetes Mellitus in Saudi Arabia.

Background: Type 2 diabetes mellitus (T2DM) is common in Saudi Arabia and represents a major health concern. Silent information regulator of transcription-1 (SIRT1) positively influences insulin sensitivity and might contribute to the pathogenesis of T2DM. This study aimed to investigate the frequency of two common functional single nucleotide polymorphisms (SNPs) in the promoter region of SIRT1; rs12778366 (T>C) and rs3758391 (T>C) in Saudi Arabian population and examine any association with T2DM.

Methods: A total of 445 volunteers were divided into 224 healthy controls and 221 patients previously diagnosed with T2DM. Genomic DNA was extracted from all samples and genotyped for SIRT1 rs12778366 and rs3758391 SNPs by TaqMan RT-PCR allelic discrimination assay. Logistic regression analysis was used to establish any relationship between these polymorphisms and T2DM.

Results: In the total study population, rs12778366 genotype frequencies were TT (89.2%), TC (10.3%), and CC (0.45%) and for the rs3758391 they were TT (16.4%), TC (44.5%), and CC (39.1%). The distribution of these genotypes, in both polymorphisms, were similar among T2DM and controls. Logistic regression analysis confirmed the lack of association between the presence of CC or CT variants and T2DM for rs12778366 and rs3758391 SNP (OR = 0.98 [CI]: 0.55 - 1.75; p = 0.999 and OR= 0.75; [CI]: 0.45 - 1.24; p = 0.313), respectively.

Conclusions: This study revealed the frequency of SIRT1 rs12778366 and rs3758391 SNPs in our population and reported no association between these polymorphisms and the risk for T2DM. This finding might add to the growing body of literature exploring the genetics of T2DM.