APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans

J Am Soc Nephrol. 2015 Nov;26(11):2882-90. doi: 10.1681/ASN.2014050469. Epub 2015 Mar 18.

Abstract

APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy-naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.

Keywords: CKD; HIV nephropathy; collapsing glomerulopathy; development; genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Associated Nephropathy / blood*
  • AIDS-Associated Nephropathy / ethnology
  • AIDS-Associated Nephropathy / genetics*
  • Adult
  • Alleles
  • Apolipoprotein L1
  • Apolipoproteins / blood*
  • Apolipoproteins / genetics*
  • Black People
  • Black or African American
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Glomerular Filtration Rate
  • Haplotypes
  • Humans
  • Inflammation
  • Linkage Disequilibrium
  • Lipoproteins, HDL / blood*
  • Lipoproteins, HDL / genetics*
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Risk Factors
  • South Africa

Substances

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