Association of HLA-DP/DQ and STAT4 polymorphisms with HBV infection outcomes and a mini meta-analysis

PLoS One. 2014 Nov 3;9(11):e111677. doi: 10.1371/journal.pone.0111677. eCollection 2014.

Abstract

Background: Though HLA-DP/DQ is regarded to associate with HBV susceptibility and HBV natural clearance, its role in hepatocellular carcinoma (HCC) development is obscure. And the role of STAT4 in HBV susceptibility and clearance as well as HCC development is still contentious. Therefore, we conducted this study, aiming to clarify these obscure relationships.

Methods: We recruited 1312 Chinese Han subjects including healthy controls, HBV carriers and HCC patients in the experiment stage. The meta-analysis included 3467 HCC patients and 5821 HBV carriers to appraise the association with HCC development.

Results: Consistent with previous studies, HLA-DP/DQ associated with HBV susceptibility and HBV natural clearance (p<0.05). However, the experiment showed that HLA-DP rs3077, rs9277535 and rs7453920 did not associate with HCC development (dominant model, rs3077, OR = 0.86, 95%CI = 0.62-1.18; rs9277535, OR = 0.94, 95%CI = 0.68-1.30; rs7453920, OR = 0.75, 95%CI = 0.44-1.27). Meta-analysis again consolidated this conclusion (allele model, rs3077, OR = 0.94, 95%CI = 0.87-1.02; rs9277535, OR = 1.04, 95%CI = 0.97-1.11; rs7453920, OR = 0.89, 95%CI = 0.76-1.02). As for STAT4 rs7574865, we did not find any significant association with HBV susceptibility (OR = 0.91, 95%CI = 0.66-1.26) or HBV natural clearance (OR = 1.13, 95%CI = 0.86-1.49). Moreover, current data failed to acquire positive connection of rs7574865 with HCC development (experiment, OR = 0.86, 95%CI = 0.62-1.19; meta-analysis, OR = 0.87, 95%CI = 0.74-1.03), which may be due to the small sample size.

Conclusions: HLA-DP/DQ polymorphisms (rs3077, rs9277535, rs7453920) did not associate with HCC development, but did correlate with HBV susceptibility and HBV natural clearance. STAT4 rs7574865 seemed not to correlate with HBV susceptibility or natural clearance. And it seemed rather ambiguous in its role on HCC development at present.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Carcinoma, Hepatocellular / genetics
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HLA-DP Antigens / genetics*
  • HLA-DQ Antigens / genetics*
  • Haplotypes
  • Hepatitis B / diagnosis
  • Hepatitis B / genetics*
  • Hepatitis B / pathology
  • Humans
  • Liver Neoplasms / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Patient Outcome Assessment
  • Polymorphism, Genetic*
  • Prognosis
  • STAT4 Transcription Factor / genetics*

Substances

  • HLA-DP Antigens
  • HLA-DQ Antigens
  • STAT4 Transcription Factor

Grants and funding

This study was funded in full by grants from Natural Science Foundation of China (grant numbers 81072443, 81100536, and 81273256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.