title: APOL1 variants associate with increased risk of CKD among African Americans.
abstract: Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.forename: Morgan
authors.initials: M
authors.lastname: Grams
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D001741:Black or African American / Q000208:ethnology*; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL