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

Abstract

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 seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold 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.

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  • Authors+Show Affiliations

    ,

    Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland, USA. jeffreyk@intra.niddk.nih.gov

    , , , , , , , , , , , , , , , , , , , , , ,

    Source

    MeSH

    AIDS-Associated Nephropathy
    Adult
    African Americans
    Age of Onset
    Apolipoprotein L1
    Apolipoproteins
    Case-Control Studies
    Disease Progression
    European Continental Ancestry Group
    Genetic Variation
    Genotype
    Glomerulosclerosis, Focal Segmental
    HapMap Project
    Human Genome Project
    Humans
    Kaplan-Meier Estimate
    Lipoproteins, HDL
    Middle Aged
    Risk Factors
    United States
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural

    Language

    eng

    PubMed ID

    21997394

    Citation

    Kopp, Jeffrey B., et al. "APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-associated Nephropathy." Journal of the American Society of Nephrology : JASN, vol. 22, no. 11, 2011, pp. 2129-37.
    Kopp JB, Nelson GW, Sampath K, et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 2011;22(11):2129-37.
    Kopp, J. B., Nelson, G. W., Sampath, K., Johnson, R. C., Genovese, G., An, P., ... Winkler, C. A. (2011). APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. Journal of the American Society of Nephrology : JASN, 22(11), pp. 2129-37. doi:10.1681/ASN.2011040388.
    Kopp JB, et al. APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-associated Nephropathy. J Am Soc Nephrol. 2011;22(11):2129-37. PubMed PMID: 21997394.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. AU - Kopp,Jeffrey B, AU - Nelson,George W, AU - Sampath,Karmini, AU - Johnson,Randall C, AU - Genovese,Giulio, AU - An,Ping, AU - Friedman,David, AU - Briggs,William, AU - Dart,Richard, AU - Korbet,Stephen, AU - Mokrzycki,Michele H, AU - Kimmel,Paul L, AU - Limou,Sophie, AU - Ahuja,Tejinder S, AU - Berns,Jeffrey S, AU - Fryc,Justyna, AU - Simon,Eric E, AU - Smith,Michael C, AU - Trachtman,Howard, AU - Michel,Donna M, AU - Schelling,Jeffrey R, AU - Vlahov,David, AU - Pollak,Martin, AU - Winkler,Cheryl A, Y1 - 2011/10/13/ PY - 2011/10/15/entrez PY - 2011/10/15/pubmed PY - 2011/12/22/medline SP - 2129 EP - 37 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 22 IS - 11 N2 - 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 seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold 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. SN - 1533-3450 UR - https://www.unboundmedicine.com/medline/citation/21997394/full_citation L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=21997394 DB - PRIME DP - Unbound Medicine ER -