Rare inborn errors associated with chronic hepatitis B virus infection

Research output: Contribution to journalJournal articlepeer-review

  • Qiang Zhao
  • Liang Peng
  • Weijun Huang
  • Qibin Li
  • Yuanyuan Pei
  • Ping Yuan
  • Lingyan Zheng
  • Yongling Zhang
  • Jia Deng
  • Cheng Zhong
  • Bin Hu
  • Hongke Ding
  • Wei Fang
  • Ru Li
  • Qijun Liao
  • Chaoshuang Lin
  • Weiping Deng
  • Huijun Yan
  • Jinghui Hou
  • Qiuliang Wu
  • And 17 others
  • Tingting Xu
  • Jinsong Liu
  • Longbo Hu
  • Tao Peng
  • Suqing Chen
  • Kar N. Lai
  • Man-Fung Yuen
  • Yue Wang
  • Mala K. Maini
  • Caixia Li
  • Miaoxin Li
  • Jian Wang
  • Xiuqing Zhang
  • Pak-Chung Sham
  • Jun Wang
  • Zhi-Liang Gao
  • Yiming Wang
Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10(-7) , 2.76 × 10(-5) , 5.08 × 10(-5) , 2.78 × 10(-4) and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10(-16) . As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively).
Original languageEnglish
JournalHepatology
Volume56
Issue number5
Pages (from-to)1661-1670
Number of pages10
ISSN0270-9139
DOIs
Publication statusPublished - 2012

ID: 46283257