TY - JOUR
T1 - APOL1 risk variants are strongly associated with HIV-associated nephropathy in black South Africans
AU - Kasembeli, Alex N.
AU - Duarte, Raquel
AU - Ramsay, Michèle
AU - Mosiane, Pulane
AU - Dickens, Caroline
AU - Dix-Peek, Thérèse
AU - Limou, Sophie
AU - Sezgin, Efe
AU - Nelson, George W.
AU - Fogo, Agnes B.
AU - Goetsch, Stewart
AU - Kopp, Jeffrey B.
AU - Winkler, Cheryl A.
AU - Naicker, Saraladevi
PY - 2015/11/1
Y1 - 2015/11/1
N2 - APOL1 variants are associatedwithHIV-associated nephropathy and FSGSinAfrican Americans. Theprevalence of these variants inAfrican populationswithCKDinHIV-1 infection has not been investigated.Wedetermined the role of APOL1 variants in 120 patients with HIV-associated nephropathy andCKD and 108 controls from a South- African black population. PatientswithCKDwere selected on the basis of histology. Genotypeswere 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 39patientswithHIV-negativeCKD), 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-SaharanAfrica.
AB - APOL1 variants are associatedwithHIV-associated nephropathy and FSGSinAfrican Americans. Theprevalence of these variants inAfrican populationswithCKDinHIV-1 infection has not been investigated.Wedetermined the role of APOL1 variants in 120 patients with HIV-associated nephropathy andCKD and 108 controls from a South- African black population. PatientswithCKDwere selected on the basis of histology. Genotypeswere 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 39patientswithHIV-negativeCKD), 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-SaharanAfrica.
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U2 - 10.1681/ASN.2014050469
DO - 10.1681/ASN.2014050469
M3 - Article
C2 - 25788523
AN - SCOPUS:84935037203
VL - 26
SP - 2882
EP - 2890
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 11
ER -