Abstract

BackgroundCervicitis 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.MethodsTen 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.ResultsT. 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.ConclusionsTLR4 and TLR9 polymorphisms, as well as haplotypes were shown to modulate the cervicitis risk.

Highlights

  • Cervicitis, i.e., the inflammation of cervix, is caused by the infections of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)

  • T. vaginalis infection was found at the highest frequency (30.7%) as compared to C. trachomatis (1.5%), N. gonorrhoeae (2.3%) and human papillomavirus (HPV) (4.6%) infections in cervicitis patients

  • TLR4 rs11536889 CC and TLR9 rs187084 TC genotypes showed the higher distribution in cervicitis patients compared to controls

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Summary

Introduction

Cervicitis, i.e., the inflammation of cervix, is caused by the infections of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Infections of Trichomonas vaginalis (TV) and human papillomavirus (HPV) have been implicated in the pathogenesis of cervicitis, in addition to other bacterial and viral pathogens [1]. Chronic inflammation is considered as a contributory factor in the development of various cancers including cervical cancer Upon infection, these pathogens activate the Toll-like Receptors (TLRs) which are one of the types of pattern recognition receptors (PRRs) present on the host innate immune cells that recognizes pathogen-associated molecular patterns (PAMPs) and stimulates antigen-specific acquired immunity for pathogen elimination [11,12,13]. 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. Variations in the Toll-like receptor genes influence susceptibility to pathogens as well as disease progression independently

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