Programmed cell death-1 3'-untranslated region polymorphism is associated with spontaneous clearance of hepatitis B virus infection

J Med Virol. 2018 Nov;90(11):1730-1738. doi: 10.1002/jmv.25265. Epub 2018 Aug 13.

Abstract

Hepatitis B virus (HBV)-specific CD8+ T cells play an important role in the clearance of HBV infection. Programmed cell death-1 (PD-1), an immunosuppressive molecule that regulates T-cell activation and peripheral immune tolerance, is increasingly shown to influence the outcome of HBV infection. rs10204525, a single-nucleotide polymorphism in the 3'-untranslated region (3'-UTR) of PD-1, has been associated with susceptibility and disease progression of chronic HBV infection in far-eastern patients. The aim of our study was to assess the impact of rs10204525 variation on HBV infection in Moroccan patients. A total of 236 patients with chronic HBV infection and 134 individuals with spontaneous HBV resolution were genotyped using a Taqman assay. In addition, PD-1 mRNA expression in peripheral blood nuclear cells was determined by quantitative reverse-transcription polymerase chain reaction. We found that the AA genotype is protective (odds ratio, 0.43; 95% confidence interval, 0.19 to 0.97; P = 0.038) against HBV infection. Interestingly, PD-1 messenger RNA (mRNA) expression analysis has revealed that chronic HBV carriers with GG and GA displayed higher levels of PD-1 mRNA compared with corresponding genotypes in resolved subjects (P = 0.031 and 0.014, respectively). Our data suggest that Mediterranean HBV-infected patients carrying PD-1 GG and GA genotypes at rs10204525 have high PD-1 mRNA expression and may be more prone to installation of chronicity.

Keywords: PD-1 polymorphism; chronic hepatitis B virus infection; programmed cell death-1; spontaneous clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Adult
  • Aged
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepatitis B / genetics*
  • Hepatitis B / immunology*
  • Hepatitis B virus / immunology*
  • Humans
  • Male
  • Middle Aged
  • Marokko
  • Polymorphism, Single Nucleotide*
  • Programmed Cell Death 1 Receptor / genetics*

Substances

  • 3' Untranslated Regions
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor