Relationship between a toll-like receptor-4 gene polymorphism, bacterial vaginosis-related flora and vaginal cytokine responses in pregnant women.
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)-1beta and IL-1 receptor antagonist (IL-1ra) concentrations in pregnant women were evaluated.


METHODS
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.


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.


CONCLUSIONS
The TLR4 896 A > G polymorphism contributes to inter-individual differences in the vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.
Genc
Mehmet R
MR
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Vardhana
Santosh
S
Delaney
Mary L
ML
Onderdonk
Andrew
A
Tuomala
Ruth
R
Norwitz
Errol
E
Witkin
Steven S
SS
D000225:Adenine; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism* / Q000382:microbiology; D011264:Pregnancy Trimesters; D011956:Receptors, Cell Surface / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014621:Vagina / Q000378:metabolism / Q000382:microbiology; D016585:Vaginosis, Bacterial / Q000378:metabolism* / Q000382:microbiology
D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D006147:Guanine; D000225:Adenine