title: A functional polymorphism in ADAR1 gene affects HBsAg seroclearance both spontaneously and interferon induced.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.forename: Weimei
authors.initials: W
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhu
authors.forename: Kangmei
authors.initials: K
authors.lastname: Chen
authors.forename: Sujun
authors.initials: S
authors.lastname: Zheng
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D055106:Genome-Wide Association Study; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007372:Interferons / Q000276:immunology*; D008156:Luciferases; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006514:Hepatitis B Surface Antigens; D016601:RNA-Binding Proteins; D007372:Interferons; D008156:Luciferases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C000595356:ADAR protein, human; D000243:Adenosine Deaminase
keywords: HBsAg seroclearance; Interferon; luciferase assays; natural clearance; qPCR