Evaluation of glutathione S-transferase GSTM1 and GSTT1 deletion polymorphisms on type-2 diabetes mellitus risk.

Abstract

BackgroundDue to the activity of GSTs in the detoxification of oxidative stress products, deletion polymorphisms of GSTM1 and GSTT1 may contribute to susceptibility to T2DM, since B-cells express very low levels of antioxidant enzymes. Recently, some studies have shown an association between GSTM1-null/GSTT1-null genotypes and an increased susceptibility to T2DM. A relationship between these polymorphisms and changes in the clinical parameters of diabetic patients has also been investigated. However, the results diverge considerably among the studies. Thus, this case-control study was designed to contribute to existing knowledge, as there are no studies on this issue performed in the Brazilian population.Methods and FindingsA total of 120 patients and 147 healthy individuals were included in this study. GSTT1 and GSTM1 deletion polymorphisms were genotyped by multiplex SYBR Green Real-Time PCR. The GSTT1-null genotype conferred a 3.2-fold increased risk to T2DM relative to the present genotype. There was no association between GSTM1-null and T2DM risk. In diabetic patients, GSTT1-null conferred higher levels of triglycerides and VLDL-cholesterol, while GSTM1-null was associated with increased levels of fasting blood glucose, glycated hemoglobin and blood pressure. We emphasized a necessity for applying log-linear analysis in order to explore an interaction between these polymorphisms properly.ConclusionThese results suggest that the GSTT1 polymorphism may play an important role in the pathogenesis of T2DM in the Brazilian population. This gene could then be added to a set of genetic markers to identify individuals with an increased risk for developing T2DM and complications associated with dyslipidemia in diabetic patients. Although there was no association of GSTM1 deletion polymorphism with susceptibility to T2DM, the influence of this polymorphism on important clinical parameters related to glycemia and blood pressure levels was verified. This finding suggests that both GSTM1-null and GSTT1-null may contribute to the clinical course of T2DM patients.