TLR2, TLR4 and TLR9 genotypes and haplotypes in the susceptibility to and clinical course of Chlamydia trachomatis infections in Dutch women

Pathog Dis. 2016 Feb;74(1):ftv107. doi: 10.1093/femspd/ftv107. Epub 2015 Nov 13.


Chlamydia trachomatis infections demonstrate remarkable differences in clinical course that are approximately 40% based on host genetic variation. Here, we study the single nucleotide polymorphisms (SNPs) and their haplotypes in TLR2, TLR4 and TLR9 (TLR2 +2477G>A; TLR2 -16934T>A; TLR4+896A>G; TLR9 -1237T>C and TLR9 +2848G>A) in relation to the susceptibility to, and severity of C. trachomatis infections. We analysed the five SNPs in a cohort of 770 Dutch Caucasian women either attending a sexually transmitted diseases outpatient clinic (n = 731) or having complaints of subfertility (n = 39). Haplotype analyses showed a trend for TLR2 haplotype I (-16934T/+2477G) to protect against the development of symptoms and tubal pathology (Ptrend = 0.03) after Chlamydia infection. In the susceptibility cohort, TLR9 haplotype III (-1237C/+2848A) showed a significant decreasing trend in the development of symptoms after C. trachomatis infection (P = 0.02, OR: 0.55, 95%CI: 0.33-0.91). Logistic regression of the TLR2 haplotypes, TLR4+896A>G, and TLR9 haplotypes showed that the TLR2 haplotype combinations AG-TA and AG-TG confer risk (OR 3.4 (P = 0.01) and 1.6 (P = 0.03)), while the TLR9 haplotype combination TG-TA protects against C. trachomatis infections (OR: 0.4, P = 0.004). Our study shows that both TLR2 and TLR9 genes and SNP combinations do influence the clinical course of Chlamydia infections.

Keywords: Chlamydia trachomatis; Clinical outcome; Immunogenetics; Toll-like receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chlamydia trachomatis / immunology*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Lymphogranuloma Venereum / genetics*
  • Lymphogranuloma Venereum / immunology
  • Lymphogranuloma Venereum / pathology
  • Netherlands
  • Polymorphism, Single Nucleotide*
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 9 / genetics*
  • White People
  • Young Adult


  • TLR2 protein, human
  • TLR4 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9