Glutathione S-Transferase Enzyme (GSTT1 and GSTM1) Gene Polymorphisms and Oxidative Stress in Egyptian Patients with End Stage Renal Disease

Abstract

Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms have been associated with the genetic susceptibility to end stage renal disease (ESRD) in different populations. We investigated the association between GSTT1 and GSTM1 genes, and ESRD in Egyptian population. The samples of 133 ESRD and 91 control subjects were collected, and their clinical characteristics were assayed. Glutathione S-transferase enzyme (GSTT1 and GSTM1) gene polymorphisms were detected by polymerase chain reaction (PCR). Serum level of malondialdehyde (MDA), the oxidative stress and lipid peroxidation biomarker, and plasma glutathione S-transferase enzyme (GST), the antioxidant enzyme, were estimated in the ESRD patients as well as in the control subjects. We demonstrated the association of MDA and GST enzyme levels with GSTT1 and GSTM1 genotypes. We investigated the association between MDA and lipid parameters in the ESRD patients. Increased of the GSTM1 deletion genotype, (GSTT1/0) and both deletion genotypes (0/0) in the ESRD patients when compared with the control subjects (P < 0.0001, OR = 3.786, 95% CI = 2.151-6.664), (P = 0.001, OR = 3.172, 95% CI = 1.595-6.308) and (P = 0.045, OR = 1.945, 95% CI = 1.009-3.749), respectively. Highly significant increase of MDA level in the ESRD patients as compared with the control subjects (P < 0.0001). Highly significant decrease of GST enzyme level in the ESRD patients as compared with the control subjects (P < 0.0001).The level of MDA is significantly increased in all GST genotypes in the ESRD patients as compared with the control group. Also, there were significant association between The genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, and high level of MDA in the ESRD patients, while the level of GST enzyme is significantly decreased in GST genotypes except the both deletion (0/0) genotypes, in which the level of GST enzyme is not significantly decreased in the ESRD patients as compared with the control subjects. There are significant association between the genetic risk factors of GSTT1 and GSTM1 genes in the ESRD, (GSTM1 null and GSTT1/0 genotypes), and low level of GST enzyme in the ESRD patients. There were significant positive correlation between MDA and total cholesterol, triglyceride, and LDL-cholesterol, and significant negative correlation between MDA and HDL-cholesterol in the ESRD patients as compared with the control subjects. In conclusion, the GSTM1 (null) genotype, (GSTT1/0) and (0/0) genotypes are independent risk factors for ESRD. The oxidative stress and lipid abnormalities are associated with ESRD in the studied Egyptian population.