Polymorphic APOBEC3 modulates chronic hepatitis B in Moroccan population.

Abstract

The cytidine deaminase apolipoprotein B mRNA editing catalytic subunit-3 (APOBEC3) induces G-to-A hypermutation in hepatitis B virus (HBV) genomes and operates as part of the innate antiviral immune system. We investigated the associations between the presence of APOBEC3 variants and HBV carriage in a case-control study in the Moroccan population. A polymorphic deletion affecting the APOBEC3B gene and the H186R variant of APOBEC3G were genotyped in 179 HBV chronic carriers and 216 healthy control subjects. In addition, to assess the overall impact of APOBEC3 deaminases on circulating HBV, we looked for hyperedited forms of the viral genome using the 3DPCR technique and analysed editing context. Data analysis showed that there was no significant difference in the frequencies of deleted APOBEC3B alleles (P = 0.261) or genotypes (P = 0.333) between patients with chronic hepatitis B and control subjects. By contrast, subjects bearing deleted genotype had a faster progression of liver disease than those with the insertion genotype (adjusted OR, 3.72; 95% CI, 0.38-36.12). The analysis of the APOBEC3G H186R polymorphism revealed that R/R genotype frequencies were not significantly different in HBV infected patients and in healthy subjects. 3DPCR was positive in 26 samples (14%) among 179. Amplified viral segments displayed monomorphic G>A transitions highly reminiscent of APOBEC3G activity. Most intriguingly, hemi/homozygous carriers of the APOBEC3B deletion had significantly lower virus loads than patients with the wild type (median 539 vs. 2213 IU/mL, P = 0.0023). This result suggests that genetic variations in APOBEC3 cytidine deaminases do not predispose to chronicity but may modulate the course of persistent HBV infection.

• Authors: S Ezzikouri, B Kitab, K Rebbani, A Marchio, S Wain-Hobson, A Dejean, J-P Vartanian, P Pineau, S Benjelloun
• Journal: Journal of viral hepatitis (J Viral Hepat) Vol. 20 Issue 10 Pg. 678-86 (Oct 2013) ISSN: 1365-2893 [Electronic] England
• PMID: 24010642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Minor Histocompatibility Antigens
• APOBEC-3G Deaminase
• APOBEC3B protein, human
• APOBEC3G protein, human
• Cytidine Deaminase

Topics

• APOBEC-3G Deaminase
• Adult
• Aged
• Carrier State (immunology)
• Cytidine Deaminase (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Hepatitis B, Chronic (genetics, immunology, pathology)
• Humans
• Male
• Middle Aged
• Minor Histocompatibility Antigens
• Morocco
• Polymorphism, Genetic