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APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.
J Am Soc Nephrol. 2011 Nov; 22(11):2129-37.JA

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.

Links

Publisher Full Text
ncbi.nlm.nih.gov
jasn.asnjournals.org
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Authors+Show Affiliations

Kopp JB
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland, USA. jeffreyk@intra.niddk.nih.gov
Nelson GW
No affiliation info available
Sampath K
No affiliation info available
Johnson RC
No affiliation info available
Genovese G
No affiliation info available
An P
No affiliation info available
Friedman D
No affiliation info available
Briggs W
No affiliation info available
Dart R
No affiliation info available
Korbet S
No affiliation info available
Mokrzycki MH
No affiliation info available
Kimmel PL
No affiliation info available
Limou S
No affiliation info available
Ahuja TS
No affiliation info available
Berns JS
No affiliation info available
Fryc J
No affiliation info available
Simon EE
No affiliation info available
Smith MC
No affiliation info available
Trachtman H
No affiliation info available
Michel DM
No affiliation info available
Schelling JR
No affiliation info available
Vlahov D
No affiliation info available
Pollak M
No affiliation info available
Winkler CA
No affiliation info available

MeSH

AIDS-Associated NephropathyAdultAfrican AmericansAge of OnsetApolipoprotein L1ApolipoproteinsCase-Control StudiesDisease ProgressionEuropean Continental Ancestry GroupGenetic VariationGenotypeGlomerulosclerosis, Focal SegmentalHapMap ProjectHuman Genome ProjectHumansKaplan-Meier EstimateLipoproteins, HDLMiddle AgedRisk FactorsUnited StatesYoung Adult

Pub Type(s)

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

Language

eng

PubMed ID

21997394

Clinical Trial Links

Determinants of Cardiovascular Disease, Kidney Disease and Diabetes

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., Friedman, D., Briggs, W., Dart, R., Korbet, S., Mokrzycki, M. H., Kimmel, P. L., Limou, S., Ahuja, T. S., Berns, J. S., Fryc, J., Simon, E. E., Smith, M. C., Trachtman, H., ... 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), 2129-37. https://doi.org/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 - https://jasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=21997394 DB - PRIME DP - Unbound Medicine ER -