CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

PloS One
Anna ReznichenkoREGaTTA (REnal GeneTics TrAnsplantation) Groningen group

Abstract

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 associa...Continue Reading

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Citations

Dec 25, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Dorothee AtzlerTanja Zeller
Sep 6, 2012·BMC Medical Genetics·Anna ReznichenkoUNKNOWN REGaTTA (REnal GeneTics TrAnsplantation) Groningen group
Mar 1, 2013·Current Pediatrics Reports·Matthew G Sampson, Harald Jüppner
Jan 8, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Erik I ChristensenHenrik Birn
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Dec 7, 2013·Clinical Journal of the American Society of Nephrology : CJASN·Afshin Parsa, Barry I Freedman
Oct 9, 2018·Current Medicinal Chemistry·Renata Kozyraki, Olivier Cases
Jul 30, 2017·BMC Research Notes·Katherine Angela BensonAmy Jayne McKnight

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Methods Mentioned

BETA
genotyping

Software Mentioned

PASW Statistics
QUANTO
BeadStudio
PolyPhen2
NanoDrop
SNAP
PLINK

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