Association of TLR4 Polymorphisms with Increased Susceptibility to Recurrent Vulvovaginal Candidiasis in Greek Women

Recurrent vulvovaginal candidiasis (RVVC) affects 5-8% of women of reproductive age. Host genetic factors, particularly single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs), may influence RVVC susceptibility by impairing vaginal mucosal antifungal immunity. The aim of this study was to assess the effect of SNPs in genes encoding TLRs on RVVC susceptibility. Τhe distribution of TLR2 Arg753Gln and TLR4 Asp299Gly/Thr399Ile polymorphisms in Greek women, including RVVC (n = 63), first-episode VVC (n = 37), Gardnerella vaginalis vaginitis (GV, n = 36) patients, and healthy controls (n = 61), was investigated using TaqMan SNP genotyping. Genotype and allele frequencies were analyzed under allelic and dominant models, with odds ratios (ORs), 95% confidence intervals (CIs), and linkage disequilibrium assessed. TLR4 Asp299Gly and Thr399Ile heterozygotes were significantly more frequent in RVVC patients compared with controls and affected RVVC susceptibility (OR: 5.57, 95% CI: 1.17-26.56, p: 0.0172; OR: 4.92, 95% CI: 1.02-23.78, p: 0.0306, respectively). No associations were observed for TLR2 Arg753Gln or for any SNP with GV or first-episode VVC. TLR4 variants co-segregated, indicating a haplotype effect. TLR4 haplotypes, rather than TLR2 polymorphism, confer increased RVVC susceptibility, supporting a genetically distinct, mucosal immunity-driven pathogenesis. Larger, ethnically diverse studies with functional assays are warranted to validate these findings and guide personalized prevention and treatment strategies.