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Inherited variations in the TLR4 immune signaling pathway are emerging as important determinants of recurrent vulvovaginal candidiasis risk, highlighting the growing role of host genetics in susceptibility to chronic fungal infections.
Although recurrent vulvovaginal candidiasis (RVVC) is common and can be highly disruptive, its tendency to return affects only certain women, even among those with comparable environmental exposures. Such variability has increasingly pointed to host immune genetics as a possible driver of susceptibility. In this study, the researchers set out to determine whether specific toll-like receptors (TLRs) polymorphisms were linked to a higher risk of RVVC in women of reproductive age.
A genetic association study was conducted involving Greek women with RVVC, first-episode VVC, Gardnerella-associated vaginitis, and healthy controls. Selected polymorphisms in TLR2 and TLR4 genes were analyzed using TaqMan single nucleotide polymorphism genotyping techniques. Genotype distributions, allele frequencies, odds ratios, and linkage patterns were subsequently evaluated using both allelic and dominant inheritance models to determine their relationship with disease susceptibility.
The analysis included 63 women with RVVC, 37 women experiencing a first episode of infection, 36 women with Gardnerella vaginitis and 61 healthy controls. The findings demonstrated a strong association between specific TLR4 variants and susceptibility to recurrent fungal infections, whereas no meaningful associations were identified for TLR2 polymorphisms (Table 1).
Further analyses showed that both TLR4 variants frequently co-occurred, suggesting that combined haplotypes rather than isolated mutations may contribute to impaired mucosal antifungal defenses. No significant relationships were noted between these polymorphisms and either first-episode VVC or Gardnerella-associated vaginitis.
The study strengthened the concept that RVVC extends beyond microbial exposure alone and may reflect an underlying host susceptibility profile driven by mucosal immune function. Identification of genetic risk markers within the TLR4 pathway may ultimately support personalized prevention strategies, risk stratification, and more targeted therapeutic approaches for women affected by recurrent disease.
Microorganisms
Association of TLR4 Polymorphisms with Increased Susceptibility to Recurrent Vulvovaginal Candidiasis in Greek Women
Maria Mavrouli et al.
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