title: Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients.
abstract: 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 of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients.
  
  
  METHODS
  GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant-antioxidant balance were determined.
  
  
  RESULTS
  Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes.
  
  
  CONCLUSIONS
  According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.
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.forename: Tatjana
authors.initials: T
authors.lastname: Damjanovic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stefanovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pekmezovic
authors.forename: Ana
authors.initials: A
authors.lastname: Savic-Radojevic
authors.forename: Marija
authors.initials: M
authors.lastname: Pljesa-Ercegovac
authors.forename: Marija
authors.initials: M
authors.lastname: Matic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Djukic
authors.forename: Vesna
authors.initials: V
authors.lastname: Coric
authors.forename: Jovana
authors.initials: J
authors.lastname: Jakovljevic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Ivanisevic
authors.forename: Steva
authors.initials: S
authors.lastname: Pljesa
authors.forename: Zorana
authors.initials: Z
authors.lastname: Jelic-Ivanovic
authors.forename: Jasmina
authors.initials: J
authors.lastname: Mimic-Oka
authors.forename: Nada
authors.initials: N
authors.lastname: Dimkovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simic
mesh_terms: D000368:Aged; D015415:Biomarkers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D005982:Glutathione Transferase