US EPA

1337302 

Journal Article 

Evidence of associations of APOBEC3B gene deletion with susceptibility to persistent HBV infection and hepatocellular carcinoma 

Zhang, T; Cai, J; Chang, J; Yu, D; Wu, C; Yan, T; Zhai, K; Bi, X; Zhao, H; Xu, J; Tan, W; Qu, C; Lin, D 

2013 

Yes 

Human Molecular Genetics
ISSN: 0964-6906
EISSN: 1460-2083 

22 

6 

1262-1269 

English 

23213177 

10.1093/hmg/dds513 

WOS:000316296600016 

APOBEC3s are a family of cytidine deaminases involved in innate cellular immunity against virus including hepatitis B virus (HBV). A germline deletion across APOBEC3A and APOBEC3B (A3B) genes results in complete removal of the A3B coding region and destroys A3B expression. To determine whether this deletion affects susceptibility to HBV infection and HBV-related hepatocellular carcinoma (HCC), A3B genotypes were analyzed in 1,124 individuals with HCC, 510 individuals with persistent HBV infection and 826 healthy controls and the association was estimated by odds ratio (OR) and 95% confidence interval (CI) computed by logistic regression. We also examined the effects of APOBEC3B on HBV genome hypermutation and replication in HCC cells. We observed a significantly higher frequency of the A3B deletion allele in persistent HBV carriers (33.3%; P=0.0015) and HCC patients (37.9%; P=1.28×10(-11)) compared with that in controls (27.5%). An increased risk for persistent HBV infection (OR=1.35, 95% CI, 1.03-1.77) and HCC development (OR=1.90, 95% CI, 1.58-2.28) was associated with at least one A3B deletion allele (+/- or -/- genotype) compared with the +/+ genotype. Transfection of A3B in HepG2 cells caused a substantial reduction of HBV RNA levels and G→A hypermutation in HBV genome. Interestingly, a cytidine deaminase null mutant of A3B (E255A) also inhibited HBV RNA production although it was unable to edit HBV. These results suggest that deletion of A3B attenuates HBV clearance, which in turn may result in persistent HBV infection and increased risk for developing HCC. Further studies are needed to verify our findings.