Background 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. Methods 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. Results 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. Conclusions 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.
|Number of pages||8|
|Journal||Nephrology Dialysis Transplantation|
|State||Published - 1 Feb 2018|
Bibliographical noteFunding Information:
Doris Duke Charitable Foundation Grant 2011035
This work was supported by NIH RO1 DK084149 and DK070941 (B.I.F.); and NIH/NIMHD R01MD007092 (M.R.P.). This work was supported by the Doris Duke Charitable Foundation Grant 2011035 (D.J.F.), and a Norman Coplon Award from Satellite Healthcare (D.J.F.); D.J.F. is a recipient of the Doris Duke CSD Award. B.I.F. and K.L.S. are co-recipients of Binational Science Foundation grant 2019223. K.L.S. is a recipient of Israel Science Foundation grant 182/15 and of research grant support from the Ernest and Bonnie Beutler Grant Research program (https://www. rambam.org.il/EnglishSite/Research/ResearchActivities/ BeutlerResearch/Pages/default.aspx).
© 2017 The Author . Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
- African American
- chronic kidney disease