Chronic Vestibulitis Is Associated with Interleukin-4 Polymorphisms Linked to Interstitial Cystitis and Atopy
Amy Schillling, Dawn Pruett, Nicky Leeborg, Terry K Morgan. Oregon Health & Science University, Portland, OR
Background: Chronic vestibulitis, also known as provoked localized vulvodynia (PLV), occurs in the rim of mucosa between the labia minora and hymen. This common disease affects approximately 15% of women during their lifetime and is the leading cause of painful intercourse. The cause is unknown, but neurogenic inflammation appears to play a key role. Neurogenic inflammation is also a shared feature with interstitial cystitis, which is present in 20% of women with PLV. Many investigators suspect a genetic basis for interstitial cystitis. However, testing for a genetic predisposition for PLV is only in the early stages of discovery. We hypothesized that PLV would be associated with the IL-4 promoter (rs22432250) and intron 2 (rs2227284) variants commonly seen in patients with interstitial cystitis and atopy.
Design: Retrospective analysis of 212 clinically confirmed cases of PLV diagnosed from 2002-2012 at Oregon Health & Science University. Subjects were classified into primary PLV (pain with first introital touch) and secondary PLV (de novo pain usually after childbirth or menopause). Clinical charts were reviewed to confirm diagnoses and screen for a history of interstitial cystitis and allergies. Since patient race may significantly affect allele frequencies, only data from non-hispanic Caucasian women were included for genetic analysis (205/212). Subject DNA was available for 195 cases (91 primary and 104 secondary). IL-4 genotypes were determined using real-time PCR-based Taqman Allelic Discrimination (ABI). Data were analyzed by X2 analysis.
Results: Secondary PLV was associated with both IL-4 variants (p<0.01) known to increase IL-4 activity and lead to elevated serum IgE levels. The allele frequency of the T-allele at -589 (promoter) was 0.20 (Caucasian controls 0.14); the allele frequency of the T-allele at 3017 (intron 2) was 0.31 (controls 0.25). IL-4 allele frequencies in primary PLV were not significantly different than controls. The prevalence of interstitial cystitis was increased in both primary and secondary PLV (32%, 27%, respectively) compared with controls (6%). The odds ratio for atopy in secondary PLV was 2.34 [1.3-4.4] (p<0.01); it was not increased in primary PLV.
Conclusions: We show for the first time that IL-4 genetic variants associated with interstitial cystitis and atopy may also play a role in secondary PLV. We have recently demonstrated that primary and secondary PLV may have different underlying causes. Our data support this working hypothesis and suggest drugs targeting the IL-4 pathway may provide a potential treatment.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 234, Tuesday Afternoon