Variation and expression of HLA-DPB1 gene in HBV infection

Immunogenetics. 2021 Jun;73(3):253-261. doi: 10.1007/s00251-021-01213-w. Epub 2021 Mar 12.

Abstract

Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10-15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.

Keywords: Disease progression; Gene expression; HLA-DPB1 gene; Hepatitis B virus; Infection susceptibility; Spontaneous virus clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • China / epidemiology
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA-DP beta-Chains / genetics*
  • Hepatitis B / epidemiology
  • Hepatitis B / genetics*
  • Hepatitis B / virology*
  • Hepatitis B virus / isolation & purification*
  • Humans
  • Meta-Analysis as Topic
  • Polymorphism, Single Nucleotide*

Substances

  • HLA-DP beta-Chains
  • HLA-DPB1 antigen