Protective role of (rs3758391 T > C) polymorphism against T2DM and its complications: Influence on GPx activity.

Background And Aims: Sirtuin-1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications.

Methods: In this case-control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for rs3758391 T > C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. genotypes were detected using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: The C allele of reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI.

Conclusions: Our findings suggest a protective role for C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease.