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

J Am Soc Nephrol. 2011 Nov;22(11):2129-37. doi: 10.1681/ASN.2011040388. Epub 2011 Oct 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • AIDS-Associated Nephropathy / ethnology*
  • AIDS-Associated Nephropathy / genetics*
  • Adult
  • Age of Onset
  • Apolipoprotein L1
  • Apolipoproteins / genetics*
  • Black or African American / genetics
  • Black or African American / statistics & numerical data
  • Case-Control Studies
  • Disease Progression
  • Genetic Variation
  • Genotype
  • Glomerulosclerosis, Focal Segmental / ethnology*
  • Glomerulosclerosis, Focal Segmental / genetics*
  • HapMap Project
  • Human Genome Project
  • Humans
  • Kaplan-Meier Estimate
  • Lipoproteins, HDL / genetics*
  • Middle Aged
  • Risk Factors
  • United States / epidemiology
  • White People / genetics
  • White People / statistics & numerical data
  • Young Adult

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Lipoproteins, HDL