title: APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans.
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.
authors: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors: Alex N
authors: AN
authors: Kasembeli
authors: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors: Raquel
authors: R
authors: Duarte
authors: Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa;
authors: Michèle
authors: M
authors: Ramsay
authors: Department of Anatomical Pathology, National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa;
authors: Pulane
authors: P
authors: Mosiane
authors: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors: Caroline
authors: C
authors: Dickens
authors: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;
authors: Thérèse
authors: T
authors: Dix-Peek
authors: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory, Leidos Biomedical Inc., Frederick, Maryland;
authors: Sophie
authors: S
authors: Limou
authors: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory, Leidos Biomedical Inc., Frederick, Maryland; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors: Efe
authors: E
authors: Sezgin
authors: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory, Leidos Biomedical Inc., Frederick, Maryland;
authors: George W
authors: GW
authors: Nelson
authors: Division of Renal Pathology/Electron Microscopy, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Agnes B
authors: AB
authors: Fogo
authors: Lancet Pathology Laboratory, Johannesburg, South Africa;
authors: Stewart
authors: S
authors: Goetsch
authors: Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland; and.
authors: Jeffrey B
authors: JB
authors: Kopp
authors: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory, Leidos Biomedical Inc., Frederick, Maryland; Saraladevi.Naicker@wits.ac.za winklerc@mail.nih.gov.
authors: Cheryl A
authors: CA
authors: Winkler
authors: Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Nephrology, University of the Witwatersrand, Johannesburg, South Africa Saraladevi.Naicker@wits.ac.za winklerc@mail.nih.gov.
authors: Saraladevi
authors: S
authors: Naicker
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics*; D044383:Black People; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006239:Haplotypes; D006801:Humans; D007249:Inflammation; D015810:Linkage Disequilibrium; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D013019:South Africa; D001741:Black or African American
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: CKD; HIV nephropathy; collapsing glomerulopathy; development; genetics