Association of glutathione S-transferase M1 and T1 gene polymorphism with oxidative stress in diabetic and nondiabetic chronic kidney disease.

BACKGROUND AND OBJECTIVE

Glutathione S-transferases (GSTs) belong to a family of ubiquitous and multifunctional enzymes that work as one of the endogenous antioxidants in our body. This study was designed to look into the association of GST polymorphism with oxidative stress in both diabetic and nondiabetic chronic kidney disease (CKD).

DESIGN AND METHODS

Three groups of patients (50 in each): diabetics without CKD (DM), diabetic CKD (DM-CKD), and nondiabetic CKD (NDM-CKD) and 50 age- and sex-matched healthy controls were recruited. Genotyping was done for GSTM1 and GSTT1 genes using a multiplex polymerase chain reaction. Serum GST and malondialdehyde (MDA) as a marker of oxidative stress were measured spectrophotometrically.

RESULTS

Based on genotyping, subjects were categorized as GSTM1+/GSTT1+, GSTM1-/GSTT1+, GSTM1+/GSTT1-, and GSTM1-/GSTT1-. Serum GST levels were lower among subjects with deletion in one/both GST genes, whereas MDA levels were found to be correspondingly raised. A negative correlation for MDA versus GST levels was observed among genotypes with one/both gene deletions. Presence of GSTM1+/GSTT1- and GSTM1-/GSTT1- was significantly higher among patients with CKD in both diabetics and nondiabetics.

INTERPRETATIONS AND CONCLUSIONS

GSTM1 and GSTT1 deletions singly or together were associated with lower GST levels and higher oxidative stress in both diabetic and nondiabetic CKD. Interestingly, GSTT1 deletion appears to be associated with both diabetic and nondiabetic CKD irrespective of the GSTM1 status.