title: Host APOL1 genotype is independently associated with proteinuria in HIV infection.
abstract: Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, are independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women's Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (≥200 mg/g) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women, 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% confidence interval (CI): 36, 108) and five-fold higher odds of proteinuria (95% CI: 2.45, 10.37) as compared with one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease.
authors.affiliation: Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Estrella
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wyatt
authors.forename: C Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.forename: Deborah
authors.initials: D
authors.lastname: Gustafson
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
mesh_terms: D000328:Adult; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D016015:Logistic Models; D008875:Middle Aged; D011507:Proteinuria / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL