DC-SIGN Polymorphisms Associate with Risk of Hepatitis C Virus Infection Among Men who Have Sex with Men but not Among Injecting Drug Users

J Infect Dis. 2018 Jan 17;217(3):353-357. doi: 10.1093/infdis/jix587.

Abstract

We aimed to identify whether genetic polymorphisms within L-SIGN or DC-SIGN correlate with hepatitis C virus (HCV) susceptibility. A men who have sex with men (MSM) and an injecting drug users (IDU) cohort of HCV cases and multiple-exposed uninfected controls were genotyped for numerous L-SIGN and DC-SIGN polymorphisms. DC-SIGN single nucleotide polymorphisms (SNPs) -139, -871, and -939 correlated with HCV acquisition in the MSM cohort only. When the same SNPs were introduced into a transcription activity assay they demonstrated a reduction in expression with predicted alteration in binding of transcription factors. DC-SIGN promoter SNPs correlated with risk of HCV acquisition via sexual but not IDU exposure, likely through modulation of mRNA expression levels.

Keywords: DC-SIGN; Hepatitis C virus; lectin; sexual transmission; single nucleotide polymorphism.

Publication types

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

MeSH terms

  • Adult
  • Cell Adhesion Molecules / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepatitis C / genetics*
  • Homosexuality, Male*
  • Humans
  • Lectins, C-Type / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Prospective Studies
  • Receptors, Cell Surface / genetics*
  • Substance Abuse, Intravenous / complications*
  • Transcription, Genetic

Substances

  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface