Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression
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 whic...
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| Format: | Article |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00053/full |
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| author | Ping An Gregory D. Kirk Sophie Limou Sophie Limou Sophie Limou Elizabeth Binns-Roemer Jeffrey B. Kopp Cheryl A. Winkler |
| author_facet | Ping An Gregory D. Kirk Sophie Limou Sophie Limou Sophie Limou Elizabeth Binns-Roemer Jeffrey B. Kopp Cheryl A. Winkler |
| author_sort | Ping An |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T09:09:14Z |
| format | Article |
| id | doaj.art-83b010fd09734221b3806b0663d7baa2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T09:09:14Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-83b010fd09734221b3806b0663d7baa22022-12-21T22:37:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-011010.3389/fimmu.2019.00053432955Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease ProgressionPing An0Gregory D. Kirk1Sophie Limou2Sophie Limou3Sophie Limou4Elizabeth Binns-Roemer5Jeffrey B. Kopp6Cheryl A. Winkler7Molecular Genetic Epidemiology Section, Basic Science Program, Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, United StatesDepartments of Epidemiology and Medicine, Johns Hopkins University, Baltimore, MD, United StatesMolecular Genetic Epidemiology Section, Basic Science Program, Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, United StatesCRTI UMR1064, Inserm, Université de Nantes & ITUN, CHU Nantes, Nantes, FranceEcole Centrale de Nantes, Nantes, FranceMolecular Genetic Epidemiology Section, Basic Science Program, Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, United StatesKidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, United StatesMolecular Genetic Epidemiology Section, Basic Science Program, Basic Research Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, United StatesApolipoprotein 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00053/fullHIV-1AIDSAPOL1host susceptibilitygenetic epidemiology |
| spellingShingle | Ping An Gregory D. Kirk Sophie Limou Sophie Limou Sophie Limou Elizabeth Binns-Roemer Jeffrey B. Kopp Cheryl A. Winkler Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression Frontiers in Immunology HIV-1 AIDS APOL1 host susceptibility genetic epidemiology |
| title | Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression |
| title_full | Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression |
| title_fullStr | Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression |
| title_full_unstemmed | Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression |
| title_short | Impact of APOL1 Genetic Variants on HIV-1 Infection and Disease Progression |
| title_sort | impact of apol1 genetic variants on hiv 1 infection and disease progression |
| topic | HIV-1 AIDS APOL1 host susceptibility genetic epidemiology |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00053/full |
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