title: Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD.
abstract: Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes-associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility.
authors.affiliation: Departments of Biochemistry, Centers for Genomics and Personalized Medicine Research and Public Health Genomics, and bfreedma@wakehealth.edu nallred@wakehealth.edu.
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.affiliation: Centers for Genomics and Personalized Medicine Research and Public Health Genomics, and.
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.affiliation: Public Health Genomics, and Biostatistical Sciences, and.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.affiliation: Public Health Genomics, and Biostatistical Sciences, and.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.affiliation: Division of Renal Medicine, Department of Medicine, Emory School of Medicine, Atlanta, Georgia;
authors.forename: Janice P
authors.initials: JP
authors.lastname: Lea
authors.affiliation: Division of Nephrology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia; and.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Kimberly
authors.affiliation: Departments of Biochemistry, Centers for Genomics and Personalized Medicine Research and.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.affiliation: Centers for Genomics and Personalized Medicine Research and Public Health Genomics, and Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina; Internal Medicine, bfreedma@wakehealth.edu nallred@wakehealth.edu.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: FSGS; development; end stage kidney disease; genetics