Association of MnSOD, CAT, and GPx1 gene polymorphism with risk of diabetic nephropathy in South Indian patients – A case control study

Abstract Purpose: Diabetic nephropathy (DN) is a remarkable complication of type 2 diabetes mellitus (T2DM), mediated by oxidative stress playing a key role. The antioxidants gene polymorphism (MnSOD, CAT, GPx1) have been interconnected to T2DM and DN. The role of these genes in the pathogenesis of DN among T2DM individuals in the South Indian population is investigated in this study. It clarifies the importance of early manifestation and reliable genetic indicators modulating the mechanism of oxidative stress in DN. Methods: The voluntary participants were divided and grouped as Group 1: Control, Group 2: T2DM without DN, and Group 3: T2DM with DN (n = 100 in each group). The levels of blood glucose, HbA1c, renal profile, plasma SOD, CAT, GPx1, MDA, and TAS were assessed. MnSOD, CAT, and GPx1 were genotyped via Tetra-arms PCR. Results: All the genotypic models of GPx1 depicts a significant role in the progression of T2DM patients with nephropathy (Co-dominant [OR: 2.134; 95%CI (1.202–3.788), p < 0.01], dominant [OR: 2.015; 95%CI (1.117–3.634), p = 0.02], and recessive model [OR: 2.215; 95%CI (1.235–3.972), p = 0.008]) but is not associated with T2DM without DN individuals; while MnSOD and CAT genotypes are not associated with the development of the disease. This data suggest that genotypes of GPx1 are at higher risk of developing DN in T2DM individuals. Moreover, MnSOD and GPx1 genotypes show significant difference in the antioxidant parameters compared to CAT genotypes. Conclusion: In contradiction to earlier studies, our study have demonstrated that compared to MnSOD and CAT genotypes, GPx1 genotypes can be considered as a influential component for higher susceptibility and risk of DN in T2DM patients among South Indian population.