Background and objective: Glutathione-S-transferase (GST) is the superfamily of genes that provides protection to the cells against reactive oxygen species and plays a vital role in phase II of biotransformation of many substances. Overexpression of GST (EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, which may be of clinical relevance. Keeping this background in mind, we have investigated the relationship between human GST gene polymorphism in end stage renal disease (ESRD) patients.
Design and methods: We have assessed 184 patients with ESRD and 569 age-and sex-matched controls from North India. The GSTT1 and GSTM1 null genotypes were identified by polymerase chain reaction (PCR). GSTP1-313 A/G mutation was determined by PCR followed by restriction enzyme digestion.
Results: The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphism were evaluated. We observed that GSTM1 null genotype was present in 46.74% of the ESRD patients while GSTT1 null genotype was present in 58.7% of the ESRD subjects. The genotypic distribution of GSTP1 was Ile(105)/Ile(105) in 47.3%, Ile(105)/Val(105) in 30.97% and Val(105)/Val(105) in 21.74% of ESRD patients. There was a significant association of null alleles of the GSTM1 (p = 0.0386; OR = 1.445, 95% CI = 1.033-2.021) and GSTT1 (p < or = 0.0001; OR = 4.568, 95% CI = 3.215-6.492) and in the -313 G alleles (Val) of the GSTP1 gene (p = 0.0032; OR = 1.956, 95% CI = 1.265-3.024) with end stage renal disease. The combined analysis of the three genotypes showed a further increased risk to ESRD (p < or = 0.0001; OR = 9.01, 95% CI = 5.55-14.626).
Interpretations and conclusions: The null / low polymorphism of the detoxifying enzymes GSTT1, GSTM1, and GSTP1 are associated with the risk of developing ESRD in North Indian patients.