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

Abstract

Objective: 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)-1β and IL-1 receptor antagonist (IL-1ra) concentrations in pregnant women were evaluated. Study design: 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-1β and IL-1ra concentrations in vaginal lavage samples were measured by ELISA. Results: 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. Conclusion: The TLR4 896 A>G polymorphism contributes to inter-individual differences in the vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.