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

Authors

  • Xiaopan Wu,

    1. 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
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    • These authors contributed equally to this work.
  • Weimei Shi,

    1. 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
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    • These authors contributed equally to this work.
  • Jia Wu,

    1. 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
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  • Xilin Zhu,

    1. 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
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  • Kangmei Chen,

    1. 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
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  • Sujun Zheng,

    1. Department of Infectious Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Zhuo Li,

    1. Artificial Liver Center, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Zhongping Duan,

    Corresponding author
    1. Department of Infectious Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
    • Correspondence

      Zhongping Duan, Artificial Liver Center, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China

      Tel: +(86) 10-63291007

      Fax: +(86) 10-63295285

      e-mail: duan2517@163.com

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  • Hui Li,

    1. Department of Epidemiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
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  • Ying Liu

    1. 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
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Abstract

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.

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