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

AbstractBACKGROUND:
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.
AuthorsKumud K Singh, Yan Wang, Kathryn P Gray, Mona Farhad, Sean Brummel, Terence Fenton, Rodney Trout, Stephen A Spector
JournalJournal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 62 Issue 2 Pg. 197-203 (Feb 01 2013) ISSN: 1944-7884 [Electronic] United States
PMID23138837 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase
Topics
  • APOBEC-3G Deaminase
  • 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

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