Association of HLA-DPA1 and HLA-DPB1 polymorphisms with spontaneous HBsAg seroclearance in Caucasians

Liver Int. 2019 Apr;39(4):646-654. doi: 10.1111/liv.14008. Epub 2019 Jan 28.

Abstract

Background & aims: Acute hepatitis B virus (HBV) infections may clear spontaneously or become chronic and run through different phases. The single nucleotide polymorphisms (SNPs) rs3077, rs9277535 and rs9277534 within the human leucocyte antigen (HLA)-DP gene have been found to be associated with HBV susceptibility and persistence in Asians. However, evidence for the influence of these variants in Caucasians has been limited so far. The aim of our study was to investigate the impact of these polymorphisms on the outcome of HBV infections in a large Caucasian population.

Methods: In this case-control study, we retrospectively analysed 1111 Caucasian individuals, including 618 with chronic HBV infections (CHB), 239 with spontaneous HBsAg seroclearance (SC) and 254 healthy controls (HC). The rs3077, rs9277535 and rs9277534 SNPs were genotyped by a polymerase chain reaction from blood samples and melting curve analysis.

Results: A significant difference in the allele distributions was observed only for the rs3077 SNP between the HC and the CHB group as well as between the SC and CHB groups. The rs3077-C allele was associated with a lower probability for spontaneous HBsAg seroclearance in comparison with the rs3077-T allele (OR 0.704, 95% CI 0.509-0.974; P = 0.033). No association of the three SNPs with the stages of chronic HBV infection was found.

Conclusion: This is the first study demonstrating an association of the rs3077-T allele with spontaneous HBsAg seroclearance in Caucasians. Further studies are needed to elucidate the role of HLA-DP variants in disease pathogenesis and their potential role for individualized disease management.

Keywords: HBsAg loss; hepatitis B; human leucocyte antigen; innate immunity; single nucleotide polymorphisms.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Germany
  • HLA-DP alpha-Chains / genetics*
  • HLA-DP beta-Chains / genetics*
  • Haplotypes
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • White People / genetics*

Substances

  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen
  • Hepatitis B Surface Antigens