APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy

Jeffrey B. Kopp, George W. Nelson, Karmini Sampath, Randall C. Johnson, Giulio Genovese, Ping An, David Friedman, William Briggs, Richard Dart, Stephen Korbet, Michele H. Mokrzycki, Paul L. Kimmel, Sophie Limou, Tejinder S. Ahuja, Jeffrey S. Berns, Justyna Fryc, Eric E. Simon, Michael C. Smith, Howard Trachtman, Donna M. MichelJeffrey R. Schelling, David Vlahov, Martin Pollak, Cheryl A. Winkler

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483 Scopus citations


Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeen-fold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-ninefold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.

Original languageEnglish (US)
Pages (from-to)2129-2137
Number of pages9
JournalJournal of the American Society of Nephrology
Issue number11
StatePublished - Nov 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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