HLA-DP and γ-interferon receptor-2 gene variants and their association with viral hepatitis activity in chronic hepatitis B infection

J Gastroenterol Hepatol. 2014 Mar;29(3):533-9. doi: 10.1111/jgh.12378.

Abstract

Background and aim: Studies show that polymorphisms in human leukocyte antigen (HLA)-DP loci and certain γ-interferon (IFN-γ) signaling pathway genes are related to persistence of hepatitis B virus (HBV) infection and viral load in chronic HBV (CHB) infection respectively. Our study aims to determine whether single-nucleotide polymorphisms (SNPs) linked to HLA-DP loci and IFN-γ signaling pathway are associated with HBV activities.

Methods: We compared the SNPs in the HLA-DPA1 gene (rs3077) and the IFN-γ receptor-2 gene (rs2284553 and rs9808753) of 100 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients with undetectable HBV DNA with 100 age- and sex-matched controls with HBV DNA > 2000 IU/mL.

Results: The median age of the study group was 47.9 years, and 61% were male patients. The distribution of the three polymorphisms was in Hardy-Weinberg equilibrium. Both rs3077 and rs2284553 polymorphisms were not associated with HBV viral load in terms of allelic frequency, genotypic frequency, dominant/recessive gene action. rs9808753 (G allele) was associated with a reduced chance of "undetectable HBV DNA" for patients below the age of 50 years in allelic frequency analysis (odds ratio 0.562; 95% confidence interval, 0.326-0.967; P value = 0.037). IFN-γ receptor-2 gene haplotype block (rs2284553/rs9808753) was not associated with HBV viral activity.

Conclusion: There was no significant association between HLA-DP polymorphism (rs3077) and IFN-γ receptor-2 gene polymorphism (rs2284553) with viral activity in HBeAg-negative CHB patients. Further studies are required to confirm the association between IFN-γ receptor-2 gene polymorphism (rs9808753) and reduced chance of having "undetectable HBV DNA" in young CHB patients.

Keywords: HLA-DP; IFN-γ pathway; chronic hepatitis B.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • DNA, Viral
  • Female
  • Gene Frequency
  • HLA-DP alpha-Chains / genetics*
  • Hepatitis B e Antigens
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Interferon gamma Receptor
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Interferon / genetics*
  • Signal Transduction / genetics
  • Viral Load / genetics*
  • Young Adult

Substances

  • DNA, Viral
  • HLA-DP alpha-Chains
  • HLA-DPA1 antigen
  • Hepatitis B e Antigens
  • Receptors, Interferon