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

Year: 2014

Authors: Rosentul D.C., Delsing C.E., Jaeger M., Plantinga T.S., Oosting M., Costantini I., Venselaar H., Joosten L.A.B., van der Meer J.W.M., Dupont B., Kullberg B.-J., Sobel J.D., Netea M.G.

Autors 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; Centre for Molecular and Biomolecular Informatics, Nijmegen Center for Molecular Life Science, Radboud University Medical Center, Nijmegen, Netherlands; Hôpital Necker-Enfants Malades, Paris, France; Department of Medicine, School of Medicine, Wayne State University, Detroit, MI, United States; Division of Infectious Diseases, Harper University Hospital, Detroit, MI, United States

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 IFN? 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.


Volume: 5      Pages from: 00483-1  to: 00483-7

KeyWords: e da rivista: gamma interferon; interleukin 10; interleukin 17; interleukin 1beta; interleukin 6; mannose binding lectin; pattern recognition receptor; toll like receptor 2; tumor necrosis factor, adult; aged; allele; Article; bioinformatics; Candida albicans; controlled study; enzyme linked immunosorbent assay; female; genetic polymorphism; genetic susceptibility; genetic variability; genotype; host resistance; human; major clinical study; middle aged; pathogenicity; peripheral blood mononuclear cell; real time polymerase chain reaction; sequence homology; single nucleotide polymorphism; vagina candidiasis; very elderly; young adult
DOI: 10.3389/fmicb.2014.00483