CLINICAL CORRELATION AND GENETIC EVALUATION OF SIRTUIN1 IN CORONARY ARTERY DISEASE AMONG SOUTH INDIAN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abstract

Background and Objective: Studies evidenced that silent information regulator 1 (SIRT1), a NAD⁺ dependent deacetylase has significant metabolic regulator, oxidative stress, and vascular function. It is involved in associations with coronary heart disease (CHD) risk and type 2 diabetes (T2D).  Single-nucleotide polymorphisms (SNPs) of SIRT1 are associated with diabetes, blood pressure (BP), cholesterol metabolism and coronary artery calcification. Our study aimed to investigate the A>G SIRT1 SNPs, (rs3818291) in association of CHD with T2DM in South Indian patients.

Methods: A case-control study was performed on 225 subjects divided into healthy controls (n=75), T2DM without CAD (n=75), and T2DM with CAD (n=75). Biochemical parameters were estimated using automated analysers. Serum Sirtuin (SIRT1) and Sestrin 2 concentrations were determined by ELISA. Genotyping of the rs3818291 polymorphism for SNP was done by PCR. Statistical investigation was done by ANOVA, chi-square test, regression, and ROC curve analysis.

Results: SIRT1 levels were significantly maximum in T2DM patients with CAD than in other groups (p<0.001). Multivariate regression analysis revealed SIRT1 as an independent predictor of CAD (adjusted OR=2.21; p=0.0019). ROC curve analysis showed excellent discriminatory ability (AUC=0.864), with an optimal cut-point of 2.804 (82.3% sensitivity and 78.5% specificity). The rs3818291 polymorphism was significantly related with CAD risk in diabetic patients, with the GG genotype being a risk factor under the recessive model (p<0.001). Although Sestrin 2 levels were increased in CAD patients, it failed to maintain its independent predictive value.

Conclusion: SIRT1 and the polymorphism rs3818291 are significantly associated with CAD in South Indian patients with T2DM. These results specify that the combination of SIRT1 biomarker analysis and genetic profiling could improve the risk assessment of CAD in this high-risk group. Further studies needed to investigate to provide a novel therapeutic approach in patients with CAD.