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.
