APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans
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Open Access
- 1 November 2015
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 26 (11), 2882-2890
- https://doi.org/10.1681/asn.2014050469
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; PAPOL1 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
This publication has 40 references indexed in Scilit:
- Genetic Variation in APOL1 Associates with Younger Age at Hemodialysis InitiationJournal of the American Society of Nephrology, 2011
- Extended high viremicsAIDS, 2011
- Y-Chromosomal Variation in Sub-Saharan Africa: Insights Into the History of Niger-Congo GroupsMolecular Biology and Evolution, 2010
- Association of Trypanolytic ApoL1 Variants with Kidney Disease in African AmericansScience, 2010
- Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 geneHuman Genetics, 2010
- The Treatment of HIV-Associated NephropathyAdvances in Chronic Kidney Disease, 2010
- Potential etiologic and functional implications of genome-wide association loci for human diseases and traitsProceedings of the National Academy of Sciences of the United States of America, 2009
- MYH9 is associated with nondiabetic end-stage renal disease in African AmericansNature Genetics, 2008
- MYH9 is a major-effect risk gene for focal segmental glomerulosclerosisNature Genetics, 2008
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006