Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy

Alice R. Goepfert, Michael Varner, Kenneth Ward, Cora Macpherson, Mark Klebanoff, Robert L. Goldenberg, Brian Mercer, Paul Meis, Jay Iams, Atef Moawad, J. Chris Carey, Kenneth Leveno, Ronald Wapner, Steve N. Caritis, Menachem Miodovnik, Yoram Sorokin, Mary J. O'Sullivan, J. Peter Van Dorsten, Oded Langer

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38 Scopus citations

Abstract

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. Study design: 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] 1β-511, IL1β Exon 5 +3954, IL6-174, IL8-845, IL10-1082, tumor necrosis factor α-238 [TNFα-238], TNFα-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 IL1β Exon 5 +3954, IL6-174, IL10-1082, and TLR-4 399 loci. Women with BV were less likely to be homozygous (C/C) for IL1β 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: IL1β 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). Conclusion: After controlling for race, polymorphisms at the IL1β Exon 5 +3954, IL6-174, and IL8-845 loci were associated with an altered rate of BV in pregnancy.

Original languageEnglish (US)
Pages (from-to)1478-1485
Number of pages8
JournalAmerican journal of obstetrics and gynecology
Volume193
Issue number4
DOIs
StatePublished - Oct 1 2005

Keywords

  • Bacterial vaginosis
  • Cytokine gene polymorphism
  • Pregnancy
  • Toll-like receptor gene polymorphism

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

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    Goepfert, A. R., Varner, M., Ward, K., Macpherson, C., Klebanoff, M., Goldenberg, R. L., Mercer, B., Meis, P., Iams, J., Moawad, A., Carey, J. C., Leveno, K., Wapner, R., Caritis, S. N., Miodovnik, M., Sorokin, Y., O'Sullivan, M. J., Van Dorsten, J. P., & Langer, O. (2005). Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy. American journal of obstetrics and gynecology, 193(4), 1478-1485. https://doi.org/10.1016/j.ajog.2005.03.053