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

Karl L. Skorecki; Jessica H. Lee; Carl D. Langefeld; Saharon Rosset; Shay Tzur; Walter G. Wasser; Revital Shemer; Gregory A. Hawkins; Jasmin Divers; Rulan S. Parekh; Man Li; Matthew G. Sampson; Matthias Kretzler; Martin R. Pollak; Shrijal Shah; Daniel Blackler; Brendan Nichols; Michael Wilmot; Seth L. Alper; Barry I. Freedman; David J. Friedman

doi:10.1093/ndt/gfw451

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

Karl L. Skorecki, Jessica H. Lee, Carl D. Langefeld, Saharon Rosset, Shay Tzur, Walter G. Wasser, Revital Shemer, Gregory A. Hawkins, Jasmin Divers, Rulan S. Parekh, Man Li, Matthew G. Sampson, Matthias Kretzler, Martin R. Pollak, Shrijal Shah, Daniel Blackler, Brendan Nichols, Michael Wilmot, Seth L. Alper, Barry I. Freedman^*David J. Friedman

^*Corresponding author for this work

School of Mathematical Sciences

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	323-330
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	33
Issue number	2
DOIs	https://doi.org/10.1093/ndt/gfw451
State	Published - 1 Feb 2018

Funding

Funders	Funder number
NIH/NIMHD	R01MD007092
National Institutes of Health	DK070941, RO1 DK084149
National Institute of Diabetes and Digestive and Kidney Diseases	P30DK081943
Doris Duke Charitable Foundation	2011035

Keywords

APOL1
APOL3
African American
FSGS
chronic kidney disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ndt/gfw451

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Skorecki, K. L., Lee, J. H., Langefeld, C. D., Rosset, S., Tzur, S., Wasser, W. G., Shemer, R., Hawkins, G. A., Divers, J., Parekh, R. S., Li, M., Sampson, M. G., Kretzler, M., Pollak, M. R., Shah, S., Blackler, D., Nichols, B., Wilmot, M., Alper, S. L., ... Friedman, D. J. (2018). A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy. Nephrology Dialysis Transplantation, 33(2), 323-330. https://doi.org/10.1093/ndt/gfw451

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title = "A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy",

abstract = "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.",

keywords = "APOL1, APOL3, African American, FSGS, chronic kidney disease",

author = "Skorecki, {Karl L.} and Lee, {Jessica H.} and Langefeld, {Carl D.} and Saharon Rosset and Shay Tzur and Wasser, {Walter G.} and Revital Shemer and Hawkins, {Gregory A.} and Jasmin Divers and Parekh, {Rulan S.} and Man Li and Sampson, {Matthew G.} and Matthias Kretzler and Pollak, {Martin R.} and Shrijal Shah and Daniel Blackler and Brendan Nichols and Michael Wilmot and Alper, {Seth L.} and Freedman, {Barry I.} and Friedman, {David J.}",

year = "2018",

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doi = "10.1093/ndt/gfw451",

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Skorecki, KL, Lee, JH, Langefeld, CD, Rosset, S, Tzur, S, Wasser, WG, Shemer, R, Hawkins, GA, Divers, J, Parekh, RS, Li, M, Sampson, MG, Kretzler, M, Pollak, MR, Shah, S, Blackler, D, Nichols, B, Wilmot, M, Alper, SL, Freedman, BI & Friedman, DJ 2018, 'A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy', Nephrology Dialysis Transplantation, vol. 33, no. 2, pp. 323-330. https://doi.org/10.1093/ndt/gfw451

TY - JOUR

T1 - A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy

AU - Skorecki, Karl L.

AU - Lee, Jessica H.

AU - Langefeld, Carl D.

AU - Rosset, Saharon

AU - Tzur, Shay

AU - Wasser, Walter G.

AU - Shemer, Revital

AU - Hawkins, Gregory A.

AU - Divers, Jasmin

AU - Parekh, Rulan S.

AU - Li, Man

AU - Sampson, Matthew G.

AU - Kretzler, Matthias

AU - Pollak, Martin R.

AU - Shah, Shrijal

AU - Blackler, Daniel

AU - Nichols, Brendan

AU - Wilmot, Michael

AU - Alper, Seth L.

AU - Freedman, Barry I.

AU - Friedman, David J.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - APOL1

KW - APOL3

KW - African American

KW - FSGS

KW - chronic kidney disease

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ER -

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

Abstract

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Keywords

UN SDGs

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