The combined effects of GSTM1/GSTT1 and MTHFR C677T polymorphisms on the systemic arterial hypertension susceptibility: A genetic association study in Brazilian diabetic patients

Abstract

This genetic association study included 150 hypertensive diabetic patients and 150 normotensives non-diabetic subjects. Glutathione S-transferases M1 and T1 (GSTM1/GSTT1) deletion polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T SNP (rs1801133) genotyping were performed by SYBR Green multiplex real-time and RFLP-PCR, respectively. Both GSTM1 and GSTT1 null (OR = 4.52, p = 0.04, and OR = 4.27, p = 0.01) and mutant (677TT) genotypes (OR = 2.95, p = 0.02) conferred risk to hypertension susceptibility. The combined genotypes (MTHFR:GSTT1:GSTM1) revealed a significant association: W/−/+, W/+/−, H/−/−, H/−/+, M/+/−, and M/+/+. These findings suggesting a probable oxidative hypothesis for hypertensive diabetic patients from the interaction of the detoxification mechanism and the homocysteine metabolism. The imbalance in antioxidant enzymes contributes to the establishment of oxidative stress in conjunction with hyperhomocysteinemia and reactive oxygen species production. We concluded that these findings suggest that both polymorphisms may contribute to hypertension susceptibility in diabetic patients.