Association of TLR4 and TLR9 gene polymorphisms and haplotypes with cervicitis susceptibility

PLoS One. 2019 Jul 31;14(7):e0220330. doi: 10.1371/journal.pone.0220330. eCollection 2019.

Abstract

Background: Cervicitis is one of the major health problems amongst women caused by infection of various pathogens including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) as well as human papillomavirus (HPV), and persistent cervical inflammation is one of the etiologic agents of cervical cancer. Toll-like receptors (TLRs) play an important role in the recognition and subsequent elimination of these pathogens. Variations in the Toll-like receptor genes influence susceptibility to pathogens as well as disease progression independently.

Methods: Ten single nucleotide polymorphisms, five each of TLR4 and TLR9 genes were analyzed among 130 cervicitis patients and 150 controls either using polymerase chain reaction-restriction fragment length polymorphism or allele specific-PCR.

Results: T. vaginalis infection was found at the highest frequency (30.7%) as compared to C. trachomatis (1.5%), N. gonorrhoeae (2.3%) and HPV (4.6%) infections in cervicitis patients. TLR4 rs11536889 CC (age-adjusted OR, 2.469 [95% CI, 1.499 to 4.065]; p < 0.001) and TLR9 rs187084 TC (age-adjusted OR, 2.165 [95% CI, 1.267-3.699]; p = 0.005) genotypes showed the higher distribution in cervicitis patients compared to controls. In addition, TLR4 rs11536889 C allele was shown to increase the risk of cervicitis (age-adjusted OR, 1.632 [95% CI, 1.132 to 2.352]; p = 0.009) compared to controls. The TLR4 haplotype GCA (OR, 0.6 [95% CI, 0.38-0.95]; p = 0.0272) and TLR9 haplotype GTA (OR, 1.99 [95% CI, 1.14-3.48]; p = 0.014) were found to be associated with decreased and increased risk of cervicitis respectively.

Conclusions: TLR4 and TLR9 polymorphisms, as well as haplotypes were shown to modulate the cervicitis risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Chlamydia trachomatis / genetics
  • Chlamydia trachomatis / isolation & purification
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Neisseria gonorrhoeae / genetics
  • Neisseria gonorrhoeae / isolation & purification
  • Odds Ratio
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 9 / genetics*
  • Trichomonas vaginalis / genetics
  • Trichomonas vaginalis / isolation & purification
  • Uterine Cervicitis / diagnosis*
  • Uterine Cervicitis / genetics
  • Uterine Cervicitis / microbiology
  • Uterine Cervicitis / virology

Substances

  • Toll-Like Receptor 4
  • Toll-Like Receptor 9

Grants and funding

This work was financially supported by Charotar University of Science and Technology (CHARUSAT) which was awarded to NJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.