Clinical EpidemiologyAPOL1 Variants Associate with Increased Risk of CKD among African AmericansFoster, Meredith C.*,†; Coresh, Josef*,†,‡,§; Fornage, Myriam‖; Astor, Brad C.¶; Grams, Morgan*,†,§; Franceschini, Nora**; Boerwinkle, Eric‖; Parekh, Rulan S.*,§,††; Kao, W.H. Linda*,† Author Information *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; †The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland; ‡Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; §Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland; ‖Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas; ¶Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; **Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina; and ††Hospital for Sick Children, University Health Network and University of Toronto, Toronto, Canada Correspondence: Dr. W.H. Linda Kao, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Room W6513, Baltimore, MD 21205. Email: [email protected] Received January 30, 2013 Accepted May 5, 2013 Journal of the American Society of Nephrology 24(9):p 1484-1491, September 2013. | DOI: 10.1681/ASN.2013010113 Buy Metrics 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. Copyright © 2013 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.