Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population

Liver Int. 2017 Oct;37(10):1476-1487. doi: 10.1111/liv.13405. Epub 2017 Mar 30.

Abstract

Background & aims: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown.

Methods: A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients.

Results: Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542.

Conclusions: This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background.

Keywords: HBV; HLA genes; Native American; genotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Argentina / epidemiology
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genotype
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • HLA-DP alpha-Chains / genetics
  • HLA-DP alpha-Chains / immunology
  • HLA-DP beta-Chains / genetics
  • HLA-DP beta-Chains / immunology
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • HLA-DQ beta-Chains / genetics
  • HLA-DQ beta-Chains / immunology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / ethnology
  • Hepatitis B, Chronic / genetics*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Host-Pathogen Interactions
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Molecular Epidemiology
  • Multivariate Analysis
  • Odds Ratio
  • Phylogeny
  • Polymorphism, Single Nucleotide*
  • Protective Factors
  • Risk Factors

Substances

  • HLA Antigens
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-Dx antigen

Associated data

  • GENBANK/KX631743
  • GENBANK/KX631919
  • GENBANK/KX641714
  • GENBANK/KX641745
  • GENBANK/KJ810920
  • GENBANK/KJ810961
  • GENBANK/KJ810930
  • GENBANK/KJ843166
  • GENBANK/KJ843195
  • GENBANK/KJ843209
  • GENBANK/KJ843217