A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese

PLoS One. 2014 Jun 18;9(6):e99724. doi: 10.1371/journal.pone.0099724. eCollection 2014.

Abstract

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Progression*
  • Ethnicity / genetics*
  • Genome-Wide Association Study*
  • Haplotypes / genetics
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology*
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results
  • Taiwan
  • Treatment Outcome

Substances

  • Hepatitis B Surface Antigens

Grants and funding

This study was supported by grants from the Chang Gung Memorial hospital (CMRPG360771-3 and CMRPG3B0221) and the National Science Council (NSC101-2314-B-182A-025-MY3 and NSC102-2314-B-001-003-MY2), Taipei Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.