A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy

Inheritance of apolipoprotein L1 gene (APOL1) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1-associated nephropathy; some studies demonstrate that heterozygotes possess excess risk fo...

Full description

Saved in:
Bibliographic Details
Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2018-02, Vol.33 (2), p.323-330
Main Authors: Skorecki, Karl L, Lee, Jessica H, Langefeld, Carl D, Rosset, Saharon, Tzur, Shay, Wasser, Walter G, Shemer, Revital, Hawkins, Gregory A, Divers, Jasmin, Parekh, Rulan S, Li, Man, Sampson, Matthew G, Kretzler, Matthias, Pollak, Martin R, Shah, Shrijal, Blackler, Daniel, Nichols, Brendan, Wilmot, Michael, Alper, Seth L, Freedman, Barry I, Friedman, David J
Format: Article
Language:English
Subjects:
Apolipoproteins L - genetics
Case-Control Studies
Genetic Predisposition to Disease
Genotype
Glomerulonephritis - genetics
Glomerulosclerosis, Focal Segmental - genetics
Humans
Kidney Failure, Chronic - genetics
Meta-Analysis as Topic
ORIGINAL ARTICLES
Polymorphism, Single Nucleotide
Prognosis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Inheritance of apolipoprotein L1 gene (APOL1) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1-associated nephropathy; some studies demonstrate that heterozygotes possess excess risk for ESKD or show earlier age at ESKD, relative to those with zero risk alleles. Nearby loci are also associated with ESKD in non-African Americans. We assessed the role of the APOL3 null allele rs11089781 on risk of non-diabetic ESKD. Four cohorts containing 2781 ESKD cases and 2474 controls were analyzed. Stratifying by APOL1 risk genotype (recessive) and adjusting for African ancestry identified a significant additive association between rs11089781 and ESKD in each stratum and in a meta-analysis [meta-analysis P  =  0.0070; odds ratio (OR) = 1.29]; ORs were consistent across APOL1 risk strata. The biological significance of this association is supported by the finding that the APOL3 gene is co-regulated with APOL1, and that APOL3 protein was able to bind to APOL1 protein. Taken together, the genetic and biological data support the concept that other APOL proteins besides APOL1 may also influence the risk of non-diabetic ESKD.
ISSN:0931-0509
1460-2385
DOI:10.1093/ndt/gfw451