Frequency of Interleukin-4 (IL-4) -589 Gene Polymorphism and Vaginal Concentrations of IL-4, Nitric Oxide, and Mannose-Binding Lectin in Women with Recurrent Vulvovaginal Candidiasis

Abstract

A C-->T substitution at position -589 in the interleukin-4 (IL-4) gene is associated with increased production of IL-4. Associations between this polymorphism and recurrent vulvovaginal candidiasis (RVVC), as well as vaginal concentrations of IL-4 and the anticandidal compounds nitric oxide (NO) and mannose binding lectin (MBL), were evaluated. Vaginal samples obtained by lavage from 42 women with RVVC during the acute stage of the disease and 43 control samples were assayed by enzyme-linked immunosorbent assay for IL-4 and NO metabolites. The -589 IL-4 gene polymorphism was detected by polymerase chain reaction and endonuclease digestion. Data were analyzed by Fisher's exact test, the nonparametric Mann-Whitney and Kruskal-Wallis tests, and Spearman rank correlation. P < .05 was considered significant. Candida albicans was identified in 38 patients with RVVC; 3 others had infection due to Candida tropicalis, and 1 had infection due to Candida krusei. The IL-4 T,T genotype was detected in 59.5% of patients with RVVC and in 7.0% of control subjects (P < .0001). The frequency of IL-4*T was 76.2% in patients with RVVC and 23.3% in control subjects (P < .0001). The median concentration of vaginal IL-4 was elevated in patients with RVVC, compared with control subjects (P < .0001). Conversely, vaginal concentrations of NO metabolites (P = .02) and MBL (P < .0001) were reduced in patients with RVVC. There was a positive association between IL-4*T homozygosity and vaginal IL-4 levels (P < .0001) and negative associations between this genotype and vaginal NO (P = .01) and MBL (P < .0001) concentrations. Reduced vaginal levels of anticandidal factors in IL-4*T homozygotes may increase susceptibility to RVVC.