TY - JOUR
T1 - Impact of APOL1 genetic variants on HIV-1 infection and disease progression
AU - An, Ping
AU - Kirk, Gregory D.
AU - Limou, Sophie
AU - Binns-Roemer, Elizabeth
AU - Kopp, Jeffrey B.
AU - Winkler, Cheryl A.
N1 - Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of health, under contract HHSN26120080001E. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and of the Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. ALIVE is supported by National Institute on Drug Abuse (U01-036297 and R01-12586). SL's work was realized in the context of the LabEx IGO program that is supported by the National Research Agency via the Investment Into The Future program (ANR-11-LABX-0016-01).
Funding Information:
This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of health, under contract HHSN26120080001E. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and of the Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. ALIVE is supported by National Institute on Drug Abuse (U01-036297 and R01-12586). SL’s work was realized in the context of the LabEx IGO program that is supported by the National Research Agency via the Investment Into The Future program (ANR-11-LABX-0016-01).
Publisher Copyright:
© 2007 - 2019 Frontiers Media S.A. All Rights Reserved.
PY - 2019
Y1 - 2019
N2 - Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication in vitro by multiple mechanisms. Coding variants in APOL1 are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which APOL1 variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of APOL1 genotypes with HIV viral load, HIV acquisition, or progression to AIDS. We assessed the role of APOL1 coding variants on HIV-1 acquisition using the conditional logistic regression test, on viral load using the t-test or ANOVA, and on progression to AIDS using Cox proportional hazards models among African Americans enrolled in the ALIVE HIV natural history cohort (n = 775). APOL1 variants were not associated with susceptibility to HIV-1 acquisition by comparing genotype frequencies between HIV-1 positive and exposed or at-risk HIV-1 uninfected groups (recessive model, 12.8 vs. 12.5%, respectively; OR 1.02, 95% CI 0.62–1.70). Similar null results were observed for dominant and additive models. APOL1 variants were not associated with HIV-1 viral load or with risk of progression to AIDS [Relative hazards (RH) 1.33, 95% CI 0.30–5.89 and 0.96, 95% CI 0.49–1.88, for recessive and additive models, respectively]. In summary, we found no evidence that APOL1 variants are associated with host susceptibility to HIV-1 acquisition, set-point HIV-1 viral load or time to incident AIDS. These results suggest that APOL1 variants are unlikely to influence HIV infection or progression among individuals of African ancestry.
AB - Apolipoprotein L1 (APOL1) has broad innate immune functions and has been shown to restrict HIV replication in vitro by multiple mechanisms. Coding variants in APOL1 are strongly associated with HIV-associated nephropathy (HIVAN) in persons with untreated HIV infection; however, the mechanism by which APOL1 variant protein potentiates renal injury in the presence of high viral load is not resolved. Little is known about the association of APOL1 genotypes with HIV viral load, HIV acquisition, or progression to AIDS. We assessed the role of APOL1 coding variants on HIV-1 acquisition using the conditional logistic regression test, on viral load using the t-test or ANOVA, and on progression to AIDS using Cox proportional hazards models among African Americans enrolled in the ALIVE HIV natural history cohort (n = 775). APOL1 variants were not associated with susceptibility to HIV-1 acquisition by comparing genotype frequencies between HIV-1 positive and exposed or at-risk HIV-1 uninfected groups (recessive model, 12.8 vs. 12.5%, respectively; OR 1.02, 95% CI 0.62–1.70). Similar null results were observed for dominant and additive models. APOL1 variants were not associated with HIV-1 viral load or with risk of progression to AIDS [Relative hazards (RH) 1.33, 95% CI 0.30–5.89 and 0.96, 95% CI 0.49–1.88, for recessive and additive models, respectively]. In summary, we found no evidence that APOL1 variants are associated with host susceptibility to HIV-1 acquisition, set-point HIV-1 viral load or time to incident AIDS. These results suggest that APOL1 variants are unlikely to influence HIV infection or progression among individuals of African ancestry.
KW - AIDS
KW - APOL1
KW - Genetic epidemiology
KW - HIV-1
KW - Host susceptibility
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UR - http://www.scopus.com/inward/citedby.url?scp=85061266368&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.00053
DO - 10.3389/fimmu.2019.00053
M3 - Article
C2 - 30733721
AN - SCOPUS:85061266368
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - JAN
M1 - 53
ER -