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Rosentul DC, Delsing CE, Jaeger M, et al. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014;5:483doi: 10.3389/fmicb.2014.00483.
Rosentul, D. C., Delsing, C. E., Jaeger, M., Plantinga, T. S., Oosting, M., Costantini, I., Venselaar, H., Joosten, L. A., van der Meer, J. W., Dupont, B., Kullberg, B. J., Sobel, J. D., & Netea, M. G. (2014). Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Frontiers in microbiology, 5483. https://doi.org/10.3389/fmicb.2014.00483
Rosentul, Diana C, et al. "Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis." Frontiers in microbiology vol. 5 (2014): 483. doi: https://doi.org/10.3389/fmicb.2014.00483
Rosentul DC, Delsing CE, Jaeger M, Plantinga TS, Oosting M, Costantini I, Venselaar H, Joosten LA, van der Meer JW, Dupont B, Kullberg BJ, Sobel JD, Netea MG. Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis. Front Microbiol. 2014 Sep 23;5:483. doi: 10.3389/fmicb.2014.00483. eCollection 2014. PMID: 25295030; PMCID: PMC4172055.
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Front Microbiol. 2014 Sep 23;5:483. doi: 10.3389/fmicb.2014.00483. eCollection 2014.

Gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis.

Frontiers in microbiology

Diana C Rosentul, Corine E Delsing, Martin Jaeger, Theo S Plantinga, Marije Oosting, Irene Costantini, Hanka Venselaar, Leo A B Joosten, Jos W M van der Meer, Bertrand Dupont, Bart-Jan Kullberg, Jack D Sobel, Mihai G Netea

Affiliations

  1. Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Center Nijmegen, Netherlands.
  2. Centre for Molecular and Biomolecular Informatics, Nijmegen Center for Molecular Life Science, Radboud University Medical Center Nijmegen, Netherlands.
  3. Hôpital Necker-Enfants Malades Paris, France.
  4. Department of Medicine, School of Medicine, Wayne State University Detroit, MI, USA ; Division of Infectious Diseases, Harper University Hospital Detroit, MI, USA.

PMID: 25295030 PMCID: PMC4172055 DOI: 10.3389/fmicb.2014.00483

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.

STUDY DESIGN: 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.

CONDENSATION: 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.

CONCLUSION: 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.

Keywords: RVVC; cytokines; genetic variation; pattern recognition receptors

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