A functional polymorphism in ADAR1 gene affects HBsAg seroclearance both spontaneously and interferon induced.

Background & Aims: Our previous study found that rs4845384 in ADAR1 gene to be associated with HBeAg seroconversion. However, the effect of rs4845384 on HBsAg seroclearance is unknown. To assess the relationship between rs4845384 and HBsAg seroclearance.

Methods: Two independent case-control studies were conducted to test whether rs4845384 in ADAR1 was associated with HBsAg clearance. Reporter gene assays and quantitative PCR experiments were also carried out to verify the functional significances of this polymorphism.

Results And Conclusions: The rs4845384 polymorphism was associated with HBsAg seroclearance both spontaneously (P = 0.028, OR = 1.36, 95% CI = 1.03-1.78) and interferon induced (P = 0.013, OR = 1.83, 95% CI = 1.13-2.96), in a total of 725 subjects. Luciferase assays showed that pGL3-rs4845384G constructs had higher expression level than pGL3-rs4845384A constructs, especially in HepG2. 2.15 cell line. Quantitative real-time RT-PCR showed that chronic hepatitis B (CHB) patients had lower ADAR1 mRNA level than healthy individuals. The AA carriers of rs4845384 had lower ADAR1 mRNA expression than non-AA carriers. The non-response susceptible allele rs4845384A was functional for regulation of ADAR1 expression, so as to influence HBsAg seroclearance of CHB patients.