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

Clin Infect Dis. 2005 May 1;40(9):1258-62. doi: 10.1086/429246. Epub 2005 Mar 11.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Reduced vaginal levels of anticandidal factors in IL-4*T homozygotes may increase susceptibility to RVVC.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Candidiasis, Vulvovaginal / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Homozygote
  • Humans
  • Interleukin-4 / genetics*
  • Interleukin-4 / metabolism*
  • Mannose-Binding Lectin / metabolism*
  • Nitric Oxide / metabolism*
  • Polymorphism, Single Nucleotide / genetics*
  • Vagina / metabolism

Substances

  • Mannose-Binding Lectin
  • Interleukin-4
  • Nitric Oxide