Association of <i>Nrf2</i>, <i>SOD2</i> and <i>GPX1</i> Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients
Djurdja Jerotic,
Marija Matic,
Sonja Suvakov,
Katarina Vucicevic,
Tatjana Damjanovic,
Ana Savic-Radojevic,
Marija Pljesa-Ercegovac,
Vesna Coric,
Aleksandra Stefanovic,
Jasmina Ivanisevic,
Zorana Jelic-Ivanovic,
Lana McClements,
Nada Dimkovic,
Tatjana Simic
Affiliations
Djurdja Jerotic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Marija Matic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Sonja Suvakov
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Katarina Vucicevic
Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
Tatjana Damjanovic
Clinical Department for Renal Diseases, Zvezdara University Medical Center, 11000 Belgrade, Serbia
Ana Savic-Radojevic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Marija Pljesa-Ercegovac
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Vesna Coric
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Aleksandra Stefanovic
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
Jasmina Ivanisevic
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
Zorana Jelic-Ivanovic
Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
Lana McClements
School of Life Sciences, Faculty of Science, University of Technology Sydney, NSW 2007 Sidney, Australia
Nada Dimkovic
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Tatjana Simic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (GSTM1) deletion polymorphism, was further analyzed. Polymorphisms in Nrf2 (rs6721961), SOD2 (rs4880), GPX1 (rs1050450), and GSTM1 were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The SOD2 Val/Val genotype increased ESRD risk (OR = 2.01, p = 0.002), which was even higher in combination with the GPX1 Leu/Leu genotype (OR = 3.27, p = 0.019). Polymorphism in SOD2 also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the Nrf2 (C/C) and GPX1 (Leu/Leu) genotypes in addition to a patients’ age and GSTM1 polymorphism. Similarly, the GPX1 (Leu/Leu) genotype contributed to longer cardiovascular survival. Conclusions: Our results show that SOD2, GPX1, and Nrf2 polymorphisms are associated with ESRD development and can predict survival.
