Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia

J Infect Dis. 2011 Oct 1;204(7):1138-45. doi: 10.1093/infdis/jir458.

Abstract

Background: Candidemia is an important cause of morbidity and mortality in critically ill patients or patients undergoing invasive treatments. Dectin-1 is the main β-glucan receptor, and patients with a complete deficiency of either dectin-1 or its adaptor molecule CARD9 display persistent mucosal infections with Candida albicans. The role of genetic variation of DECTIN-1 and CARD9 genes on the susceptibility to candidemia is unknown.

Methods: We assessed whether genetic variation in the genes encoding dectin-1 and CARD9 influence the susceptibility to candidemia and/or the clinical course of the infection in a large cohort of American and Dutch candidemia patients (n = 331) and noninfected matched controls (n = 351). Furthermore, functional studies have been performed to assess the effect of the DECTIN-1 and CARD9 genetic variants on cytokine production in vitro and in vivo in the infected patients.

Results: No significant association between the single-nucleotide polymorphisms DECTIN-1 Y238X and CARD9 S12N and the prevalence of candidemia was found, despite the association of the DECTIN-1 238X allele with impaired in vitro and in vivo cytokine production.

Conclusions: Whereas the dectin-1/CARD9 signaling pathway is nonredundant in mucosal immunity to C. albicans, a partial deficiency of β-glucan recognition has a minor impact on susceptibility to candidemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group / genetics
  • Alleles
  • CARD Signaling Adaptor Proteins / genetics*
  • Candidemia / ethnology
  • Candidemia / etiology*
  • Candidemia / genetics
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Interferon-gamma / blood
  • Interleukins / blood
  • Lectins, C-Type
  • Leukocytes, Mononuclear / metabolism
  • Membrane Proteins / genetics*
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Signal Transduction / genetics
  • Tumor Necrosis Factor-alpha / blood

Substances

  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • Interleukins
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Tumor Necrosis Factor-alpha
  • dectin 1
  • Interferon-gamma