title: 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 variantGSTO2 GGgenotype were at 2.45-fold higher risk of ESRD development compared to the wild typeGSTO2 AAgenotype (OR=2.45; 95%CI=1.18-5.07; p=0.016). The results ofGSTO1/GSTO2haplotype analysis showed that the haplotype combination ofGSTO1(*A)/GSTO2(*A) (GSTO1variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least oneGSTO1reference 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.
authors.affiliation: Serbian Chamber of Biochemists.
authors.forename: Slavica
authors.initials: S
authors.lastname: Cimbaljevic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Suvakov
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
authors.affiliation: Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pekmezovic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Radic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Coric
authors.affiliation: Clinical Department for Renal Diseases, Zvezdara University Medical Center, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Damjanovic
authors.affiliation: Clinical Department for Renal Diseases, Zvezdara University Medical Center, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Dimkovic
authors.affiliation: Department of Nephrology and Hemodialysis, University Teaching Hospital Zemun, Belgrade, Serbia.
authors.forename: Rodoljub
authors.initials: R
authors.lastname: Markovic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
authors.affiliation: Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
keywords: end-stage renal disease; genetic polymorphism; glutathione S-transferase; oxidative stress