Association of GSTO1 and GSTO2 polymorphism with risk of end-stage renal disease development and patient survival

Abstract

Background: Oxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients. Methods: A total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month). Results: Individuals carrying the variant GSTO2 GG genotype were at 2.45-fold higher risk of ESRD development compared to the wild type GSTO2 AA genotype (O R=2.45; 95%CI = 1.18-5.07; p=0.016). The results of GSTO1/GSTO2 haplotype analysis showed that the haplotype combination of GSTO1 (*A)/GSTO2 (*A) (GSTO1 variant/GSTO2 wild type allele) was protective for ESRD (O R= 0.23 95% CI=0.12-0.44, p=0.001). Patients carrying at least one GSTO1 reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122). Conclusions: GSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients' survival.

Keywords

• end-stage renal disease
• genetic polymorphism
• glutathione s-transferase
• oxidative stress