title: Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis.
abstract: OBJECTIVE
  Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for pattern recognition receptors (PRRs) on susceptibility to RVVC.
  
  
  METHODS
  For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects.
  
  
  RESULTS
  Single nucleotide polymorphisms (SNPs) in TLR1, TLR4, CLEC7A, and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His) increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in silico analysis, and in vitro functional assays suggested that it reduces production of IL-17 and IFNγ upon stimulation of peripheral blood mononuclear cells with Candida albicans. No effects were observed on serum mannose-binding lectin concentrations.
  
  
  CONCLUSIONS
  This study demonstrates the association of susceptibility to RVVC with genetic variation in TLR2, most likely caused by decreased induction of mucosal antifungal host defense.
  
  
  CONCLUSIONS
  Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rosentul
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Corine E
authors.initials: CE
authors.lastname: Delsing
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Jaeger
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Irene
authors.initials: I
authors.lastname: Costantini
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Nijmegen Center for Molecular Life Science, Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Hanka
authors.initials: H
authors.lastname: Venselaar
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Hôpital Necker-Enfants Malades Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dupont
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.affiliation: Department of Medicine, School of Medicine, Wayne State University Detroit, MI, USA ; Division of Infectious Diseases, Harper University Hospital Detroit, MI, USA.
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sobel
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
keywords: RVVC; cytokines; genetic variation; pattern recognition receptors