Effect of GSTM1 and GSTT1 Deletions in the Development of Oxidative Stress in Children with Chronic Kidney Disease

Journal of Clinical and Basic Cardiology 2013; 16 (1-4): 1-5

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Keywords: children,  chronic kidney disease,  gene polymorphism,  GSTM1,  GSTT1,  homocysteine,  oxidative stress

Background: Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S transferases (GST) are involved in the detoxification of xenobiotics and protection from oxidative damage. We hypothesized that genetic polymorphisms in antioxidant enzymes GSTM1 and GSTT1 are more frequent in ESRD and modulate the degree of oxidative stress in these patients. Objectives: The present study was designed to evaluate oxidized LDA (ox-LDL), high-sensitivity C-reactive protein (hs-CRP), and homocysteine (hcy) levels in children with end-stage renal disease (ESRD) treated with maintenance haemodialysis (MHD) or under conservative treatment, to compare these levels with those assayed in control subjects, and to evaluate these levels with different GSTM1 and GSTT1 genotypes. Methods: This case-control study was conducted in 78 children. They were divided into 3 groups: group I (44 on HD), group II (14 on conservative treatment), and group III (20 normal healthy children) served as controls. All enrolled cases and controls were subjected to genotyping for GSTM1 and GSTT1 by polymerase chain reaction (PCR) and determination of ox-LDL, hs-CRP, and hcy levels. Results: Oxidized LDL levels were significantly higher in both the MHD and conservative treatment groups than in controls and levels were higher in the MHD group than in the conservative treatment group (199.48 ± 78.63 µ/l, 182.07 ± 128.77 µ/l, and 88.25 ± 23.02 µ/l, respectively). hs-CRP levels were significantly higher in the MHD group compared to the control group (4.03 ± 4.59 mg/dl and 1.14 ± 0.75 mg/dl). Homocysteine showed significantly higher levels in the MHD group when compared to both conservative treatment and control groups (73.43 ± 35.08, 20.35 ± 32.81 µmol/ml, and 5.9 ± 2.8 µmol/ml, respectively). Dialyzed and conservative-treatment patients had significantly higher frequencies of the GSTM1 and GSTT1 null genotypes when compared to the control group. Conclusion: Patients with GSTM1 or GSTT1 null genotypes are more vulnerable to oxidative stress compared with those who possess normal gene expression in chronic kidney disease.