Document Detail


Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children.
MedLine Citation:
PMID:  23138837     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Apolipoprotein B mRNA editing catalytic polypeptide 3G (APOBEC3G) protein is incorporated into nascent virus particles and mediates cytidine deamination (C-to-U) of first-strand reverse transcripts of HIV-1 in target cells resulting in G-to-A hypermutation of the coding strand and premature degradation. We investigated the effects of APOBEC3G genetic variants on HIV-1-related disease in children.
METHODS: APOBEC3G variants were detected using real-time polymerase chain reaction in HIV-1-infected children from Pediatric AIDS Clinical Trials Group (PACTG) protocols P152 and P300 that evaluated the effectiveness of 3 mono- or dual-nucleoside reverse transcriptase inhibitor treatments.
RESULTS: Of the 1049 children evaluated, 60% were non-Hispanic black, 26% Hispanic, 13% non-Hispanic white, and 1% other or unknown race/ethnicity. Age ranged from 42 days to 18 years; 45% were males. APOBEC3G-H186R homozygous G/G genotype was associated with more rapid HIV-1 disease progression [hazard ratio (HR): 1.69; P = 0.01] and central nervous system (CNS) impairment (HR: 2.00; P = 0.02) compared with the wild-type A/A or heterozygous A/G genotype in a recessive model. In both additive and dominant models, APOBEC3G-F119F-C allele was associated with protection against disease progression (HR [additive]: 0.69; P = 0.002 and HR [dominant]: 0.60; P = 0.001, respectively) and CNS impairment (HR [additive]: 0.65; P = 0.02 and HR [dominant]: 0.54; P = 0.007, respectively). These associations remained significant in multivariate analyses controlling for baseline characteristics or previously identified genetic variants known to alter HIV-1-related disease in this cohort of children.
CONCLUSIONS: APOBEC3G-H186R and F119F variants are associated with altered HIV-1-related disease progression and CNS impairment in children.
Authors:
Kumud K Singh; Yan Wang; Kathryn P Gray; Mona Farhad; Sean Brummel; Terence Fenton; Rodney Trout; Stephen A Spector
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  62     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-03-08     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  IM; X    
Affiliation:
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA. kusingh@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Central Nervous System Diseases / genetics*,  virology
Child
Child, Preschool
Cytidine Deaminase / genetics*
Disease Progression
Disease-Free Survival
Female
Genotype
HIV Infections / complications,  genetics*
HIV-1*
Humans
Infant
Kaplan-Meier Estimate
Male
Multivariate Analysis
Polymorphism, Single Nucleotide
Grant Support
ID/Acronym/Agency:
1R01NS077874/NS/NINDS NIH HHS; 5 U01 AI41110/AI/NIAID NIH HHS; 5R01MH085608/MH/NIMH NIH HHS; N01-DK-9-001/HHSN267200800001C/DK/NIDDK NIH HHS; R01 MH085608/MH/NIMH NIH HHS; R01 NS077874/NS/NINDS NIH HHS; U01 AI068616/AI/NIAID NIH HHS; U01 AI068632/AI/NIAID NIH HHS; U01 AI068632/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
EC 3.5.4.5/APOBEC3G protein, human; EC 3.5.4.5/Cytidine Deaminase
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