Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.

Human Genetics
Shay TzurKarl Skorecki

Abstract

MYH9 has been proposed as a major genetic risk locus for a spectrum of nondiabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African-specific missense mutations (S342G and I384M) in the neighboring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. The APOL1 gene product, apolipoprotein L-1, has been studied for its roles in trypanosomal lysis, autophagic cell death, lipid metabolism, as well as vascular and other biological activities. We also show that the distribution of these newly identified APOL1 risk variants in African populations is consistent with the pattern of African ancestry ESKD risk previously attributed to MYH9.Mapping by admixture linkage disequilibrium (MALD) localized an interval on chromosome 22, in a region that includes the MYH9 gene, which was shown to contain African ancestry risk variants associated with certain forms of ESKD (Kao et al. 2008; Kopp et al. 2008). MYH9 encodes nonmuscle myosin heavy chain IIa, a major cytoskeletal nanomotor protein expressed in many cell types, including podocyte cells of the renal glomerulus. Moreover, 39 different coding reg...Continue Reading

References

Jan 3, 2001·Journal of the American Society of Nephrology : JASN·Giovanni CandianoGian Marco Ghiggeri
Mar 7, 2003·Nature·Luc VanhammeEtienne Pays
Jun 10, 2004·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Michele CarraroLuigi Faccini
Dec 27, 2005·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Doron M BeharKarl Skorecki
Feb 3, 2006·Genetics·Wolfgang StephanCharles H Langley
May 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gabriel BedoyaAndrés Ruiz-Linares
Jul 19, 2006·Cellular and Molecular Life Sciences : CMLS·B Vanhollebeke, E Pays
May 29, 2008·The Journal of Biological Chemistry·Guanghua WanChien-an A Hu
Sep 17, 2008·Nature Genetics·W H Linda KaoUNKNOWN Family Investigation of Nephropathy and Diabetes Research Group
Sep 17, 2008·Nature Genetics·Jeffrey B KoppCheryl A Winkler
Oct 18, 2008·Autophagy·Siqin ZhaorigetuChien-an A Hu
Jul 2, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Barry I FreedmanDonald W Bowden
Mar 5, 2010·The Journal of Clinical Investigation·Björn HartlebenTobias B Huber
Mar 20, 2010·Clinical Journal of the American Society of Nephrology : CJASN·Meredith A Bostrom, Barry I Freedman

❮ Previous
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Citations

May 9, 2012·Cellular and Molecular Life Sciences : CMLS·Peter A Doris
Mar 1, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Murli U PurswaniUNKNOWN IMPAACT 219/219C Study Team
Jun 5, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Hae Il CheongJohannes Schlondorff
Sep 8, 2012·International Urology and Nephrology·Bamidele O TayoRichard S Cooper
May 11, 2012·Current Diabetes Reports·Nicholette D Palmer, Barry I Freedman
Nov 10, 2011·Current Hypertension Reports·Barry I Freedman, Mariana Murea
Jul 31, 2013·Current Rheumatology Reports·Teresa K Chen, Derek M Fine
Oct 5, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julius Lukeš, Jayne Raper
Aug 6, 2011·Nature Medicine·Stuart J Shankland, Martin R Pollak
Jul 10, 2013·Nature Reviews. Genetics·Teri A Manolio
May 4, 2011·Nature Reviews. Nephrology·Saharon RossetKarl Skorecki
Jun 30, 2011·Nature Reviews. Nephrology·Paul E Drawz, John R Sedor
Feb 27, 2013·Nature Reviews. Nephrology·Giulio GenoveseMartin R Pollak
Nov 12, 2013·The New England Journal of Medicine·Winfred W Williams, Martin R Pollak
Nov 12, 2013·The New England Journal of Medicine·Afshin ParsaUNKNOWN CRIC Study Investigators
Dec 1, 2011·Sexual Health·Claire NaftalinFrank A Post
Mar 25, 2011·Human Molecular Genetics·Conall M O'SeaghdhaW H Linda Kao
Jan 11, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Florian Kronenberg
Jan 20, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Wenrong ChengHong Zhang
Oct 5, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jessica N CookeDonald W Bowden
Sep 21, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Barry I FreedmanJohn S Parks
Feb 24, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Shay TzurWalter G Wasser
Feb 4, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Barry I Freedman, Carl D Langefeld
Jul 19, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Amy Jayne McKnightAlexander P Maxwell
Apr 27, 2011·Current Opinion in HIV and AIDS·John Phair, Frank Palella
Jan 20, 2012·Current Opinion in Nephrology and Hypertension·Martin R PollakDavid J Friedman
Mar 16, 2011·Molecular and Cellular Biology·Duncan B JohnstoneLawrence B Holzman
Oct 5, 2011·American Journal of Nephrology·Doron M BeharKarl Skorecki
Apr 11, 2012·Public Health Genomics·S M FullertonW Burke
Nov 28, 2013·American Journal of Nephrology·Barry I FreedmanNancy M P King
Sep 2, 2011·The Journal of Clinical Investigation·David J Friedman, Martin R Pollak
Sep 13, 2011·PloS One·Maija WessmanUNKNOWN FinnDiane Study Group
Jan 10, 2013·PloS One·Duncan B JohnstoneLawrence B Holzman
Mar 22, 2013·PloS One·Konstantinos VoskaridesConstantinos Deltas
Oct 15, 2011·Journal of the American Society of Nephrology : JASN·Sethu M MadhavanJohn R Sedor
Oct 15, 2011·Journal of the American Society of Nephrology : JASN·Jeffrey B KoppCheryl A Winkler
Oct 15, 2011·Journal of the American Society of Nephrology : JASN·Natalia PapetaAli G Gharavi
Oct 15, 2011·Journal of the American Society of Nephrology : JASN·David J FriedmanMartin R Pollak
Dec 3, 2011·Journal of the American Society of Nephrology : JASN·Derek M FineKarl Skorecki

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BETA
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