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Open AccessArticle

Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients

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Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
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Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
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Clinical Department for Renal Diseases, Zvezdara University Medical Center, 11000 Belgrade, Serbia
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Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
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School of Life Sciences, Faculty of Science, University of Technology Sydney, NSW 2007 Sidney, Australia
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Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(7), 431; https://doi.org/10.3390/toxins11070431
Received: 3 June 2019 / Revised: 15 July 2019 / Accepted: 18 July 2019 / Published: 23 July 2019
(This article belongs to the Special Issue Immune Dysfunction in Uremia)
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. View Full-Text
Keywords: end-stage renal disease; hemodialysis; survival; Nrf2; SOD2; GPX1; polymorphism; oxidative stress end-stage renal disease; hemodialysis; survival; Nrf2; SOD2; GPX1; polymorphism; oxidative stress
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Jerotic, D.; Matic, M.; Suvakov, S.; Vucicevic, K.; Damjanovic, T.; Savic-Radojevic, A.; Pljesa-Ercegovac, M.; Coric, V.; Stefanovic, A.; Ivanisevic, J.; Jelic-Ivanovic, Z.; McClements, L.; Dimkovic, N.; Simic, T. Association of Nrf2, SOD2 and GPX1 Polymorphisms with Biomarkers of Oxidative Distress and Survival in End-Stage Renal Disease Patients. Toxins 2019, 11, 431.

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