Association of TLR4 and TLR9 gene polymorphisms with cervical HR-HPV infection status in Chinese Han population

Abstract

Background Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. Methods A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case–control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR–RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan–Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. Results The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan–Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). Conclusion Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.

Relationship of Toll-Like Receptor 7, 9, and 10 Polymorphisms and the Severity of Coronavirus Disease 2019

“…The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent and multiple high-risk human papillomavirus infection in Chinese Han population (29). In addition, a significantly higher frequency of the rs187084 C allele was observed in Epstein Barr virus negative infected healthy subjects (30). Patients with TLR9 rs187084 C allele and TC, CC genotype have higher risk for COVID-19 in our study.…”

Recognition ofChlamydia trachomatisby Toll-Like Receptor 9 is altered during persistence

“…TLR9 haplotypes and polymorphisms have been previously shown to correlate with potential risk of cervicitis 35 , cervical cancer 71 , as well as susceptibility and the development of symptoms after HR-HPV and C. trachomatis infection 36,72 . TLR9-stimulatory adjuvants have also been used extensively in chlamydial vaccine development 73–77 .…”

“…Given its origin 69 (and re-emergence 70 ) as a murine lung pathogen, C. muridarum likely evolved under heightened selective pressure in this environment and the reduced stimulatory potential of its gDNA may be evidence of a pathoadaptation to this niche. TLR9 haplotypes and polymorphisms have been previously shown to correlate with potential risk of cervicitis 35 , cervical cancer 71 , as well as susceptibility and the development of symptoms after HR-HPV and C. trachomatis infection 36,72 . TLR9stimulatory adjuvants have also been used extensively in chlamydial vaccine development [73][74][75][76][77] .…”

Involvement of TLR9 in priming the immune response in oral papillomatosis induced by low-risk HPV

“…For most subjects, HPV-associated lesions are cleared within 1–2 years [ 67 ]. Another study showed that the median HR-HPV clearance time was 10.5 months [ 66 , 67 , 68 , 69 ].…”

“…In the absence of a correlation between TLR9 immune signal and macrophage number, we suppose that other immune determinants may be assessed, such as TLR4, another important PRR involved in the immune response in HPV [ 57 , 68 , 71 ], and DCs, as professional APCs.…”