Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese

Nat Commun. 2016 May 31;7:11664. doi: 10.1038/ncomms11664.

Abstract

Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10(-12)). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Carrier Proteins / genetics*
  • Carrier Proteins / immunology
  • Case-Control Studies
  • Cell Line
  • Chromosomes, Human, Pair 8 / genetics*
  • Female
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Hepatitis B Surface Antigens / isolation & purification
  • Hepatitis B virus / isolation & purification
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Hepatocytes
  • Humans
  • Interferon Regulatory Factor-3 / immunology
  • Interferon Regulatory Factor-3 / metabolism
  • Liver / cytology
  • Liver / immunology
  • Liver / virology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Serologic Tests
  • Viral Load / immunology
  • Virus Replication / immunology
  • Young Adult

Substances

  • Carrier Proteins
  • Hepatitis B Surface Antigens
  • INTS10 protein, human
  • IRF3 protein, human
  • Interferon Regulatory Factor-3