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Genetic association of Toll-like receptor 4 with cervical cytokine concentrations during pregnancy

Genes & Immunity volume 10, pages 636–640 (2009)Cite this article

Abstract

Toll-like receptors (TLRs) are critical components of innate immunity, recognizing bacterial microorganisms and initiating local inflammatory responses. In this study, we assessed the impact of genetic variation in TLR genes on cervical concentrations of pro- and anti-inflammatory cytokines, and determined whether this relationship is influenced by bacterial vaginosis (BV). A total of 4 single nucleotide polymorphisms (SNPs) in TLR2 and 12 in TLR4 were examined for associations with 10 cervical pro- and anti-inflammatory cytokine concentrations in 91 African-American (AA) and 97 European-American (EA) women in the first trimester of pregnancy. In EAs, individuals with the TT genotype at rs1554973 (TLR4) had higher cervical concentrations of interleukin-1 beta (IL-1b) compared with those with the CT or TT genotypes (P=1.5 × 10−5), which remains significant after correction for multiple testing. This association was more significant in women with BV (P=5 × 10−3) than those without BV (P=0.02). This SNP was also associated with cervical concentrations of IL-1a, IL-6, IL-8 and IP10 (interferon-gamma-inducible protein 10) (P=6 × 10−3, 0.03, 0.05, 6 × 10−3, respectively). Our study demonstrates that TLR4 is an important mediator of pro-inflammatory cervical immune responses, particularly in EA women and especially in those with microbial disorders such as BV.

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Acknowledgements

We would like to acknowledge funding support by the NICHD 1 R01 HD41 663–01A1, 1 R01 HD052732–01 and MO1-RR000056.

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Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA

    K K Ryckman & S M Williams

  2. Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    M A Krohn & H N Simhan

  3. Division of Reproductive Infectious Diseases and Immunology, Magee Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    M A Krohn & H N Simhan

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  1. K K Ryckman
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  2. S M Williams
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  4. H N Simhan
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Correspondence to S M Williams.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Ryckman, K., Williams, S., Krohn, M. et al. Genetic association of Toll-like receptor 4 with cervical cytokine concentrations during pregnancy. Genes Immun 10, 636–640 (2009). https://doi.org/10.1038/gene.2009.47

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