Research
Basic science: Gynecology
Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome

https://doi.org/10.1016/j.ajog.2008.10.039Get rights and content

Objective

Patients with vulvar vestibulitis syndrome (VVS) and control subjects were tested for a polymorphism in the gene coding for the NALP3 component of inflammasomes, cytoplasmic structures regulating interleukin (IL)-1β production.

Study Design

DNA from 143 women with VVS and 182 control women were tested for a length polymorphism in intron 4 of the gene (CIAS1) that codes for NALP3. Vestibular tissue was examined for NALP3 expression. Whole blood cultures were tested for Candida albicans-induced IL-1β production.

Results

The allele 12 frequency was higher in control subjects than in the patients with VVS (P = .02). Among patients with VVS and a self-reported history of recurrent vulvovaginal candidiasis (RVVC), the allele 7 frequency was 43.9% as compared with 30.8% in patients with no history of RVVC and 26.9% in control women (P = .035 vs other patients and .001 vs control subjects). NALP3 was identified in vestibular tissue. C albicans-induced IL-1β production was reduced in samples from women with the 7,7 genotype (P = .030).

Conclusion

Polymorphism in the CIAS1 gene may play a central role in the triggering of VVS in a subset of patients.

Section snippets

Materials and Methods

The study population consisted of 143 women with VVS. The control subjects were 182 sexually active women with no history of vulvodynia; they did not undergo a gynecologic examination. All subjects were white. Patients with VVS were identified as having severe pain confined to the vulvar vestibule on light contact with a cotton swab, intense pain on attempted sexual intercourse or tampon insertion, variable degrees of vestibular erythema, and duration of symptoms for at least 6 months. Other

Results

The 4 CIAS1 alleles were combined into 10 different genotypes (Table 1). The distributions were in Hardy-Weinberg equilibrium. In both patients and control subjects the 12,12 genotype was the most prevalent whereas allele 6 was the least prevalent. The 12,12 genotype was found in a higher percentage of control subjects (47.8%) than in patients with VVS (35.7%) (P = .031). Similarly, the allele 12 frequency was 63.2% in control subjects as opposed to 54.2% in patients with VVS (P = .024).

Comment

Homozygosity for the 12 repeat unit of the CIAS1 length polymorphism was the most prevalent genotype in control women and women with VVS. Because this genotype is associated with the highest level of NALP3 production and NALP3 is the rate-limiting step in inflammasome formation9, 13 it appears that the 12,12 genotype is optimal for inflammasome function. Possession of allele 7, which contains 200 fewer bp than allele 12, may result in formation of an altered NALP3-containing inflammasome or an

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    Cite this article as: Lev-Sagie A, Prus D, Linhares IM, et al. Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2009;200:303.e1-303.e6.

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