Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy.
OBJECTIVE
This study was undertaken to estimate the frequency of inflammatory cytokine and Toll-like receptor gene polymorphisms in women with and without bacterial vaginosis (BV) in pregnancy.


METHODS
A secondary analysis was performed of pregnant women at less than 30 weeks' gestation enrolled as part of 2 multicenter studies. Eight hundred eighty-five women were assessed for BV (defined as Nugent's vaginal Gram stain score 7-10 and a pH > 4.5). Comparisons were made between women with or without BV. Extracted maternal DNA was analyzed for 7 cytokine (interleukin [IL] 1beta-511, IL1beta Exon 5 +3954, IL6-174, IL8-845, IL10-1082, tumor necrosis factor alpha-238 [TNFalpha-238], TNFalpha-308) and 2 Toll-like receptor (TLR-4 299, TLR-4 399) gene polymorphisms.


RESULTS
BV was diagnosed in 497 women and 388 did not have BV. Genotype and allele frequency analyses revealed associations with BV and polymorphisms at the IL1beta Exon 5 +3954, IL6-174, IL10-1082, and TLR-4 399 loci. Women with BV were less likely to be homozygous (C/C) for IL1beta Exon 5 +3954 (P = .04). Women with BV were also less likely to have polymorphisms at the IL10-1082 (P = .03) and TLR-4 399 (P = .04) loci in the univariate analysis. Women with BV were more likely to be heterozygous (G/C) for the IL6-174 genotype (P < .0001). Multivariate analysis, controlling for maternal race, confirmed the following associations with BV: IL1beta Exon 5 +3954 (odds Ratio [OR] 0.5, 95% CI 0.3-0.9) and IL6-174 (OR 2.2, 95% CI 1.6-3.1). In addition, polymorphism at the IL8-845 locus was associated with a decreased risk for BV (OR 0.6, 95% CI 0.4-1.0).


CONCLUSIONS
After controlling for race, polymorphisms at the IL1beta Exon 5 +3954, IL6-174, and IL8-845 loci were associated with an altered rate of BV in pregnancy.
Goepfert
Alice R
AR
Department of Obstetrics and Gynecology, The University of Alabama, Birmingham, AL, USA.
Varner
Michael
M
Ward
Kenneth
K
Macpherson
Cora
C
Klebanoff
Mark
M
Goldenberg
Robert L
RL
Mercer
Brian
B
Meis
Paul
P
Iams
Jay
J
Moawad
Atef
A
Carey
J Chris
JC
Leveno
Kenneth
K
Wapner
Ronald
R
Caritis
Steve N
SN
Miodovnik
Menachem
M
Sorokin
Yoram
Y
O'Sullivan
Mary J
MJ
Van Dorsten
J Peter
JP
Langer
Oded
O
D000328:Adult; D001424:Bacterial Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D018121:Receptors, Cytokine / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*; D014621:Vagina / Q000166:cytology / Q000276:immunology*; D014623:Vaginal Diseases / Q000276:immunology / Q000382:microbiology*
D018121:Receptors, Cytokine; D051193:Toll-Like Receptors