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J Acquir Immune Defic Syndr. 2013 Feb 1;62(2):197-203. doi: 10.1097/QAI.0b013e31827ab612.

Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children.

Author information

1
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA. kusingh@ucsd.edu

Abstract

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.

PMID:
23138837
PMCID:
PMC3658306
DOI:
10.1097/QAI.0b013e31827ab612
[Indexed for MEDLINE]
Free PMC Article

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