Glutathione peroxidase, superoxide dismutase and catalase genotypes and activities and the progression of chronic kidney disease

Nephrol Dial Transplant. 2011 Sep;26(9):2806-13. doi: 10.1093/ndt/gfq828. Epub 2011 Feb 16.

Abstract

Background: Oxidative stress has been linked to the progression of disease, including chronic kidney disease (CKD). The aim of the present study was to determine the association between single-nucleotide polymorphisms (SNPs) of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase and their activities and the progression of CKD.

Methods: This is a prospective cohort study of 185 CKD patients (Stages 2-4), followed for up to 12 months. All patients were genotyped for SNPs of SOD (SOD Ala16Val), GPx (GPx Pro197Leu) and catalase (C-262T). The rate of change over the study period of estimated glomerular filtration rate (eGFR), plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities were determined.

Results: CKD patients with the SOD Ala/Val and Val/Val genotypes had a significantly greater eGFR decline compared to those with the Ala/Ala genotype (Ala/Val compared with Ala/Ala odds ratio (OR) 0.35, 95% CI 0.19 to 0.64, P = 0.001; Val/Val compared with Ala/Ala OR 0.25, 95% CI 0.10 to 0.65, P = 0.005). The progression of CKD was not associated with SNPs of the GPx or catalase genes studied but there was a direct relationship between the rate of change of plasma GPx activity and the rate of change of eGFR over 12 months (P = 0.025).

Conclusion: CKD patients with the SOD Ala/Val and Val/Val genotypes have a greater decline in kidney function than those with the Ala/Ala genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Catalase / genetics*
  • Catalase / metabolism
  • Cohort Studies
  • Disease Progression
  • Erythrocytes / enzymology
  • Female
  • Follow-Up Studies
  • Genotype
  • Glomerular Filtration Rate
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase / metabolism
  • Humans
  • Kidney Failure, Chronic / enzymology*
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Survival Rate

Substances

  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase