Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00483/full |
| _version_ | 1831642627778281472 |
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| author | Diana eRosentul Corine eDelsing Martin eJaeger Theo ePlantinga Marije eOoosting Irene eConstantini Hanka eVenselaar Leo eJoosten Jos WM Van Der Meer Bertrand eDupont Bart-Jan eKullberg Jack eSobel Mihai eNetea |
| author_facet | Diana eRosentul Corine eDelsing Martin eJaeger Theo ePlantinga Marije eOoosting Irene eConstantini Hanka eVenselaar Leo eJoosten Jos WM Van Der Meer Bertrand eDupont Bart-Jan eKullberg Jack eSobel Mihai eNetea |
| author_sort | Diana eRosentul |
| collection | DOAJ |
| description | 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 C. albicans. No effects were observed on serum MBL concentrations.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. |
| first_indexed | 2024-12-19T12:45:45Z |
| format | Article |
| id | doaj.art-8810d170585f487f8d15b1005bbb16aa |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-19T12:45:45Z |
| publishDate | 2014-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-8810d170585f487f8d15b1005bbb16aa2022-12-21T20:20:47ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2014-09-01510.3389/fmicb.2014.00483112607Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal CandidiasisDiana eRosentul0Corine eDelsing1Martin eJaeger2Theo ePlantinga3Marije eOoosting4Irene eConstantini5Hanka eVenselaar6Leo eJoosten7Jos WM Van Der Meer8Bertrand eDupont9Bart-Jan eKullberg10Jack eSobel11Mihai eNetea12RadboudUMCRadboudUMCRadboudUMCRadboudUMCRadboudUMCRadboudUMCRadboudUMCRadboudUMCRadboudUMCHopital NeckerRadboudUMCWayne State UniversityRadboudUMCObjective. 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 C. albicans. No effects were observed on serum MBL concentrations.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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00483/fullCytokinesGenetic VariationPolymorphism, Single NucleotidePattern Recognition ReceptorsRVVC |
| spellingShingle | Diana eRosentul Corine eDelsing Martin eJaeger Theo ePlantinga Marije eOoosting Irene eConstantini Hanka eVenselaar Leo eJoosten Jos WM Van Der Meer Bertrand eDupont Bart-Jan eKullberg Jack eSobel Mihai eNetea Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis Frontiers in Microbiology Cytokines Genetic Variation Polymorphism, Single Nucleotide Pattern Recognition Receptors RVVC |
| title | Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis |
| title_full | Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis |
| title_fullStr | Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis |
| title_full_unstemmed | Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis |
| title_short | Gene Polymorphisms in Pattern Recognition Receptors and Susceptibility to Idiopathic Recurrent Vulvovaginal Candidiasis |
| title_sort | gene polymorphisms in pattern recognition receptors and susceptibility to idiopathic recurrent vulvovaginal candidiasis |
| topic | Cytokines Genetic Variation Polymorphism, Single Nucleotide Pattern Recognition Receptors RVVC |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2014.00483/full |
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