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CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage r...

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Autores principales: Reznichenko, Anna, Snieder, Harold, van den Born, Jacob, de Borst, Martin H., Damman, Jeffrey, van Dijk, Marcory C. R. F., van Goor, Harry, Hepkema, Bouke G., Hillebrands, Jan-Luuk, Leuvenink, Henri G. D., Niesing, Jan, Bakker, Stephan J. L., Seelen, Marc, Navis, Gerjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344899/
https://www.ncbi.nlm.nih.gov/pubmed/22574174
http://dx.doi.org/10.1371/journal.pone.0036512
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author Reznichenko, Anna
Snieder, Harold
van den Born, Jacob
de Borst, Martin H.
Damman, Jeffrey
van Dijk, Marcory C. R. F.
van Goor, Harry
Hepkema, Bouke G.
Hillebrands, Jan-Luuk
Leuvenink, Henri G. D.
Niesing, Jan
Bakker, Stephan J. L.
Seelen, Marc
Navis, Gerjan
author_facet Reznichenko, Anna
Snieder, Harold
van den Born, Jacob
de Borst, Martin H.
Damman, Jeffrey
van Dijk, Marcory C. R. F.
van Goor, Harry
Hepkema, Bouke G.
Hillebrands, Jan-Luuk
Leuvenink, Henri G. D.
Niesing, Jan
Bakker, Stephan J. L.
Seelen, Marc
Navis, Gerjan
author_sort Reznichenko, Anna
collection PubMed
description Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys.
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spelling pubmed-33448992012-05-09 CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation Reznichenko, Anna Snieder, Harold van den Born, Jacob de Borst, Martin H. Damman, Jeffrey van Dijk, Marcory C. R. F. van Goor, Harry Hepkema, Bouke G. Hillebrands, Jan-Luuk Leuvenink, Henri G. D. Niesing, Jan Bakker, Stephan J. L. Seelen, Marc Navis, Gerjan PLoS One Research Article Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys. Public Library of Science 2012-05-04 /pmc/articles/PMC3344899/ /pubmed/22574174 http://dx.doi.org/10.1371/journal.pone.0036512 Text en Reznichenko et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reznichenko, Anna
Snieder, Harold
van den Born, Jacob
de Borst, Martin H.
Damman, Jeffrey
van Dijk, Marcory C. R. F.
van Goor, Harry
Hepkema, Bouke G.
Hillebrands, Jan-Luuk
Leuvenink, Henri G. D.
Niesing, Jan
Bakker, Stephan J. L.
Seelen, Marc
Navis, Gerjan
CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title_full CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title_fullStr CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title_full_unstemmed CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title_short CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation
title_sort cubn as a novel locus for end-stage renal disease: insights from renal transplantation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3344899/
https://www.ncbi.nlm.nih.gov/pubmed/22574174
http://dx.doi.org/10.1371/journal.pone.0036512
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