Serum SIRT1 Levels and Genetic Variants in Diabetic Nephropathy: Insights from a Cross-sectional study

Abstract

The aim of the study was to compare sirtuin 1 serum levels in non-insulin dependent diabetics and diabetic nephropathy patients, and evaluate the pattern of polymorphism of SIRT 1 gene in these patients, and find the relation between polymorphism of SIRT1 gene and sirtuin1 serum levels in diabetic nephropathy patients and those with various stages of diabetic nephropathy. Methodology: 108 type-2 diabetic patients without complications as controls and 108 diabetic nephropathy patients as the case group were included in the study. SIRT 1 expression was measured by ELISA, and SIRT1 gene polymorphism was analyzed using the PCR-RFLP method. Results: The mean serum sirtuin 1 level were significantly lower in diabetic nephropathy patients compared to controls (p=0.000). The distribution of genotypes did not conform to Hardy-Weinberg equilibrium. The frequency of the wild-type genotype (AA) was higher in the case group, while the mutant allele (AG+GG) was more prevalent in controls. The distribution of genotypes did not conform to Hardy-Weinberg equilibrium (chi-square =7.203, p=0.027). There was no significant association observed between SIRT1 gene polymorphism and serum sirtuin 1 level in diabetic nephropathy patients(p=0.001). Additionally, no significant difference was found in serum sirtuin 1 level between different stages of diabetic nephropathy based on albuminuria testing and estimated glomerular filtration rate (eGFR)(p=0.33). Conclusion: Patients with diabetic nephropathy exhibited significantly lower serum sirtuin 1 level compared to controls, suggesting a potential role of sirtuin 1 in the pathogenesis of DN. We also conclude that serum SIRT 1 expression may be used as a diagnostic marker. The results indicate a need for further research to better understand the role of SIRT1 in diabetic nephropathy and its potential as a biomarker or therapeutic target for this condition.