Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection

Sci Rep. 2017 Nov 20;7(1):15843. doi: 10.1038/s41598-017-16011-2.

Abstract

Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries. We confirmed two previously reported significant associations, in the IL28B/IFNL4 and the major histocompatibility complex (MHC) regions, with spontaneous clearance in the European population. We further fine-mapped the association in the MHC to a region of about 50 kilo base pairs, down from 1 mega base pairs in the previous study. Additional analyses suggested that the association in MHC is stronger in samples from North America than those from Europe.

MeSH terms

  • Europe
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity
  • Hepatitis C / genetics*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Major Histocompatibility Complex / genetics*
  • Male
  • North America
  • Polymorphism, Single Nucleotide / genetics

Substances

  • IFNL3 protein, human
  • IFNL4 protein, human
  • Interleukins
  • Interferons