Relationship between a toll-like receptor-4 gene polymorphism, bacterial vaginosis-related flora and vaginal cytokine responses in pregnant women

Department of Obstetrics and Gynecology, Cornell University, Итак, New York, United States
European Journal of Obstetrics & Gynecology and Reproductive Biology (Impact Factor: 1.7). 11/2004; 116(2):152-6. DOI: 10.1016/j.ejogrb.2004.02.010
Source: PubMed


The relationship between a single nucleotide polymorphism (TLR4 896 A > G) in the toll-like receptor-4 (TLR4) gene, qualitative and quantitative changes in vaginal micro-flora and vaginal interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1ra) concentrations in pregnant women were evaluated.
Qualitative and quantitative microbial methods were used to characterize vaginal micro-flora of 238 women at 18-22 weeks gestation. Polymerase chain reaction was used to determine TLR4 genotype. IL-1beta and IL-1ra concentrations in vaginal lavage samples were measured by ELISA.
The TLR4 variant was identified in 10.3% of women. Carriage of this variant was associated with a median increase in vaginal pH (P = 0.05), a greater than 10-fold increase in vaginal Gardnerella vaginalis levels (P < 0.0001) and a 10-fold increase in the vaginal concentration of three species of anaerobic Gram-negative rods, Prevotella, Bacteroides, and Porphyromonas (P = 0.08 ). Colonization with G. vaginalis and/or the anaerobic Gram-negative rods resulted in elevated vaginal IL-1 (P = 0.01) and IL-1ra (P < 0.0002) concentrations in women who were TLR4 896A homozygotes, but not in TLR4 896G carriers.
The TLR4 896 A > G polymorphism contributes to inter-individual differences in the vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.

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    • "For example, TLR-4 genes have been implicated in BV, PD and IBD pathogenesis (98–100). Cytokine-producing genes such as IL-1β and IL-1RA have been involved in the pathogenesis of BV, PD, IBD and PS (43, 101–104). Levels of pro-inflammatory cytokines such as TNF-α are increased in CD, PD and PS (27, 105, 106). "
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