Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 26, Issue 11, Pages 2882-2890Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2014050469
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Funding
- National Institutes of Health (NIH) Fogarty International Center [1D43TW008330-01A1]
- National Institute of Diabetes and Digestive and Kidney Diseases
- Non-communicable Chronic Diseases Leadership Training Program
- Medical Research Council of South Africa
- National Research Foundation of South Africa
- National Health Laboratory Service Research Trust
- Columbia University-South Africa Training Program for Research on AIDS-Related Malignancies
- NIH National Cancer Institute [1D43CA153715-03, HHSN26120080001E]
- Division of Nephrology of University of the Witwatersrand
- Faculty Research Committee individual grant, University of the Witwatersrand
- NIH National Cancer Institute Center for Cancer Research
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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 SouthAfrican 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 polynnorphisms, 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-naive 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.
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