APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy

• Published in: Journal of the American Society of Nephrology Vol. 22; no. 11; pp. 2129 - 2137
• Main Authors: Kopp, Jeffrey B., Nelson, George W., Sampath, Karmini, Johnson, Randall C., Genovese, Giulio, An, Ping, Friedman, David, Briggs, William, Dart, Richard, Korbet, Stephen, Mokrzycki, Michele H., Kimmel, Paul L., Limou, Sophie, Ahuja, Tejinder S., Berns, Jeffrey S., Fryc, Justyna, Simon, Eric E., Smith, Michael C., Trachtman, Howard, Michel, Donna M., Schelling, Jeffrey R., Vlahov, David, Pollak, Martin, Winkler, Cheryl A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society of Nephrology 01.11.2011
• Subjects: Adult; Age of Onset; AIDS-Associated Nephropathy - ethnology; AIDS-Associated Nephropathy - genetics; Apolipoprotein L1; Apolipoproteins - genetics; Biological and medical sciences; Black or African American - genetics; Black or African American - statistics & numerical data; Case-Control Studies; Clinical Research; Disease Progression; Genetic Variation; Genotype; Glomerulonephritis; Glomerulosclerosis, Focal Segmental - ethnology; Glomerulosclerosis, Focal Segmental - genetics; HapMap Project; Human Genome Project; Human viral diseases; Humans; Infectious diseases; Kaplan-Meier Estimate; Lipoproteins, HDL - genetics; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Risk Factors; United States - epidemiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; White People - genetics; White People - statistics & numerical data; Young Adult; United States; Glomerulonephritis; Kidney disease; Immunopathology; Nephrology; Urinary system disease; Genetic variant; Retroviridae; AIDS; Immune deficiency; Lentivirus; Urology; Infection; Virus; Viral disease; Nephrotic syndrome with focal glomerular sclerosis; Human immunodeficiency virus
• ISSN: 1046-6673; 1533-3450; 1533-3450
• DOI: 10.1681/ASN.2011040388

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.