title: Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to candidemia.
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.
authors: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors: Diana C
authors: DC
authors: Rosentul
authors: Theo S
authors: TS
authors: Plantinga
authors: Marije
authors: M
authors: Oosting
authors: William K
authors: WK
authors: Scott
authors: Digna R
authors: DR
authors: Velez Edwards
authors: P Brian
authors: PB
authors: Smith
authors: Barbara D
authors: BD
authors: Alexander
authors: John C
authors: JC
authors: Yang
authors: Gregory M
authors: GM
authors: Laird
authors: Leo A B
authors: LA
authors: Joosten
authors: Jos W M
authors: JW
authors: van der Meer
authors: John R
authors: JR
authors: Perfect
authors: Bart-Jan
authors: BJ
authors: Kullberg
authors: Mihai G
authors: MG
authors: Netea
authors: Melissa D
authors: MD
authors: Johnson
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D058387:Candidemia / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044465:White People / Q000235:genetics; D000099181:Dectin-1
chemical_list: D053468:CARD Signaling Adaptor Proteins; D007371:Interferon-gamma; D007378:Interleukins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D000099181:Dectin-1; C505855:CARD9 protein, human