A meta-analysis of mannose-binding lectin gene polymorphisms with the risk of recurrent vulvovaginal infections.

The genetic variants of Mannose-Binding Lectin, a vital component of innate immunity have been studied with acute/recurrent vaginal infections ((R)VVI) and presented inconclusive findings. Therefore, a systematic review and meta-analysis of published data were conducted to assess the possible role of these variations in (R)VVI. A comprehensive search was made using PubMed, Web of Science and Google scholar till June 18, 2019. A total of 12 studies met the specified criteria and were included in the analysis. Different comparisons were made on the basis of the outcome of interest that resulted in the filtering of studies for the pooled analysis to find an association using the standard genetic models. Odds ratio (OR) with 95% confidence interval (CI) was chosen as the effect measure for the data synthesis. The trim and fill technique was applied to adjust the publication bias. The meta-analysis revealed the significant association (p < 0.05) of rs1800450 polymorphism with RVVI risk (OR ≥ 3.5) in all the genetic models. The subgroup analysis identified the same association in Caucasian and Mixed ethnicity. Quantitative synthesis based on RVVC showed>3.5 fold risk of disease development accredited to rs1800450. A combined evaluation of Exon1 variants showed no association with (R)VVI. This meta-analysis suggests rs1800450 polymorphism as a genetic predisposing factor for RVVI, but to reinforce, further studies with a larger sample size are warranted.

A Comprehensive in Silico Analysis of Regulatory SNPs of Human CLEC7A Gene and Its Validation as Genotypic and Phenotypic Disease Marker in Recurrent Vulvovaginal Infections.

Recurrent Vulvovaginal infections (RVVI) are the commonly reported microbiological syndrome affecting millions of women globally. Various molecules of innate immune system are instrumental in clearance of these microbial pathogens, thus suggested as one of the most important contributing factor in determining the disease outcome. Dendritic cell-associated C-type lectin-1 (Dectin-1) is an important molecule of innate immunity that is primarily known for its role in antifungal defenses. However, role of dectin-1 in recognition of other pathogens is also documented. The intracellular expression of dectin-1 was shown to be up-regulated by Mannose Binding Lectin (MBL)-mediated opsonophagocytosis of pathogens. Dectin-1 is encoded by CLEC7A, postulated to be a candidate gene in modulating risk of developing RVVI. In this study, we identified CLEC7A causal variants using in silico analysis. To assess their impact on susceptibility to RVVI, these causal variants along with serum dectin-1 levels (sDectin-1) were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Enzyme Linked Immnosorbent Assay (ELISA) respectively, under a case-control design. Furthermore, effect of these polymorphisms was also assessed on sMBL levels. In silico analysis revealed 9 putative functional conserved SNPs of CLEC7A. Association analysis revealed a significantly lower risk of developing RVVI and its types in carriers of CLEC7A rs3901533 G allele and its homozygous genotypes (p < 0.05). The heterozygous genotype was associated with significant protection against RVVI (p = 0.004). Haplotypes GGG and GTA showed significant protection against RVVI (p < 0.0001; p = 0.0003), Bacterial Vaginosis (p = 0.03; p = 0.002), Vulvovaginal Candidiasis (p = 0.03; p = 0.01) and Mixed Infections (p = 0.007; p = 0.04). Mean sDectin-1 levels were significantly high in RVVI and its types compared to controls (p < 0.05). Further, genotype-phenotype stratification showed significant differences within/between cases groups and controls. The CLEC7A rs3901533 polymorphism was also found to be associated with sMBL levels. The present study contributed novel insights into the role of dectin-1 in RVVI. CLEC7A rs3901533 polymorphism and high sDectin-1 levels along with low sMBL levels were found to be associated with RVVI susceptibility. Thus, screening of women with RVVI for these novel associations may lead to better diagnosis and treatment. Also genotyping method used in this study constitutes a simple and reliable assay, which can be confidently, used as a cheaper alternative for genotyping these variants in clinical settings. Finally, new restorative markers for other infectious diseases might be found by exploring nine functionally identified CLEC7A SNPs.

Are you a lumper or a splitter?

The current goal of evidence-based medicine, prospective therapeutic interventions in large numbers of patients, may not always reach an accurate conclusion. Individual variations in genetic characteristics need to be acknowledged and taken into account in the analysis. Some women with recurrent vulvo-vaginal candiosis (RVVC) have polymorphisms in genes that directly contribute to their increased susceptibility to these infections. Similarly, genetic polymorphism analyses of mother and fetus, along with highly sensitive non-culture methods of microbial detection, have identified patients at elevated risk for premature labor and delivery. Utilization of more complete information provides the basis for more specific and individualized therapeutic interventions.

Interleukin-1beta gene polymorphism in women with vulvar vestibulitis syndrome.

OBJECTIVE: The pathogenesis of vulvar vestibulitis syndrome remains unknown but may be related to a localized chronic inflammation. The relation between this syndrome and a polymorphism at position +3953 in the interleukin-1beta gene was examined. Allele 2 of this gene has been associated with increased pro-inflammatory immunity. STUDY DESIGN: Buccal or vestibular swabs from 59 women with strictly defined vulvar vestibulitis and from 48 healthy women were tested by polymerase chain reaction for the presence of two alleles at the +3953 interleukin-1beta locus. RESULTS: Allele 2 of the interleukin-1beta gene was identified in 27 (46%) women with vulvar vestibulitis as opposed to 12 (25%) control women (P=0.03). The interleukin-1beta 1,1 genotype was present in 36 (75%) controls as opposed to 32 (54%) vulvar vestibulitis syndrome patients (P=0.02). All subjects had been previously tested for induced interleukin-1beta production in response to bacterial lipopolysaccharide. In both patients and controls, possession of allele 2 was associated with a small but non-statistically significant increase in induced interleukin-1beta production. CONCLUSION: Allele 2 in the interleukin-1beta gene is more common in women with vulvar vestibulitis syndrome than in other women. Susceptibility to vulvar vestibulitis syndrome might be influenced by carriage of this polymorphism.

Familial allergic seminal vulvovaginitis.

Vulvovaginal reactions to seminal fluid occurred in all four women in a family. The reactions consisted of stinging, burning, and pain in the vagina, starting during coitus or immediately after ejaculation, and persisting for 2 to 72 hours. The vagina and vulva were red and swollen, with urticaria on the labia. Although skin tests showed a positive reaction in two of three women tested, no sperm agglutination antibody was detected. Benadryl was effective in preventing the development of vulvovaginal reactions completely in one woman and partially in two others.