title: 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.
authors: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland, USA. jeffreyk@intra.niddk.nih.gov
authors: Jeffrey B
authors: JB
authors: Kopp
authors: George W
authors: GW
authors: Nelson
authors: Karmini
authors: K
authors: Sampath
authors: Randall C
authors: RC
authors: Johnson
authors: Giulio
authors: G
authors: Genovese
authors: Ping
authors: P
authors: An
authors: David
authors: D
authors: Friedman
authors: William
authors: W
authors: Briggs
authors: Richard
authors: R
authors: Dart
authors: Stephen
authors: S
authors: Korbet
authors: Michele H
authors: MH
authors: Mokrzycki
authors: Paul L
authors: PL
authors: Kimmel
authors: Sophie
authors: S
authors: Limou
authors: Tejinder S
authors: TS
authors: Ahuja
authors: Jeffrey S
authors: JS
authors: Berns
authors: Justyna
authors: J
authors: Fryc
authors: Eric E
authors: EE
authors: Simon
authors: Michael C
authors: MC
authors: Smith
authors: Howard
authors: H
authors: Trachtman
authors: Donna M
authors: DM
authors: Michel
authors: Jeffrey R
authors: JR
authors: Schelling
authors: David
authors: D
authors: Vlahov
authors: Martin
authors: M
authors: Pollak
authors: Cheryl A
authors: CA
authors: Winkler
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000208:ethnology* / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D017668:Age of Onset; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D014644:Genetic Variation; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000208:ethnology* / Q000235:genetics*; D060148:HapMap Project; D016045:Human Genome Project; D006801:Humans; D053208:Kaplan-Meier Estimate; D008075:Lipoproteins, HDL / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL