Association of Nrf2, SOD2 and GPX1 polymorphisms with biomarkers of oxidative distress and survival in end-stage renal disease patients

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

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

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Publication Type:: Journal Article
Citation:: Toxins, 2019, 11 (7)
Issue Date:: 2019-07-23

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Field	Value	Language
dc.contributor.author	Jerotic, D https://orcid.org/0000-0002-1664-6557	en_US
dc.contributor.author	Matic, M	en_US
dc.contributor.author	Suvakov, S	en_US
dc.contributor.author	Vucicevic, K https://orcid.org/0000-0001-9676-5785	en_US
dc.contributor.author	Damjanovic, T	en_US
dc.contributor.author	Savic-Radojevic, A	en_US
dc.contributor.author	Pljesa-Ercegovac, M	en_US
dc.contributor.author	Coric, V	en_US
dc.contributor.author	Stefanovic, A	en_US
dc.contributor.author	Ivanisevic, J	en_US
dc.contributor.author	Jelic-Ivanovic, Z	en_US
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014	en_US
dc.contributor.author	Dimkovic, N	en_US
dc.contributor.author	Simic, T https://orcid.org/0000-0001-8683-5129	en_US
dc.date.available	2019-07-18	en_US
dc.date.issued	2019-07-23	en_US
dc.identifier.citation	Toxins, 2019, 11 (7)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/135630
dc.description.abstract	© 2019 by the authors. 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.	en_US
dc.relation.ispartof	Toxins	en_US
dc.relation.isbasedon	10.3390/toxins11070431	en_US
dc.title	Association of Nrf2, SOD2 and GPX1 polymorphisms with biomarkers of oxidative distress and survival in end-stage renal disease patients	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	11	en_US
utslib.for	0604 Genetics	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	11	en_US

Abstract:

© 2019 by the authors. 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.

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http://hdl.handle.net/10453/135630