1887

Abstract

Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig–McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.052811-0
2013-08-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/8/1858.html?itemId=/content/journal/jgv/10.1099/vir.0.052811-0&mimeType=html&fmt=ahah

References

  1. Carvalho A., Pasqualotto A. C., Pitzurra L., Romani L., Denning D. W., Rodrigues F. 2008; Polymorphisms in Toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis 197:618–621 [View Article][PubMed]
    [Google Scholar]
  2. Carvalho A., Osório N. S., Saraiva M., Cunha C., Almeida A. J., Teixeira-Coelho M., Ludovico P., Pedrosa J., Pitzurra L. other authors 2011; The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation. PLoS ONE 6:e28256 [View Article][PubMed]
    [Google Scholar]
  3. Carvalho A., Cunha C., Almeida A. J., Osório N. S., Saraiva M., Teixeira-Coelho M., Pedreiro S., Torrado E., Domingues N. other authors 2012; The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma. Genes Immun 13:197–201 [View Article][PubMed]
    [Google Scholar]
  4. Corr S. C., O’Neill L. A. 2009; Genetic variation in Toll-like receptor signalling and the risk of inflammatory and immune diseases. J Innate Immun 1:350–357 [View Article][PubMed]
    [Google Scholar]
  5. Daud I. I., Scott M. E., Ma Y., Shiboski S., Farhat S., Moscicki A. B. 2011; Association between Toll-like receptor expression and human papillomavirus type 16 persistence. Int J Cancer 128:879–886 [View Article][PubMed]
    [Google Scholar]
  6. Ferguson R., Ramanakumar A. V., Richardson H., Tellier P. P., Coutlée F., Franco E. L., Roger M. 2011; Human leukocyte antigen (HLA)-E and HLA-G polymorphisms in human papillomavirus infection susceptibility and persistence. Hum Immunol 72:337–341 [View Article][PubMed]
    [Google Scholar]
  7. Franco E., Villa L., Rohan T., Ferenczy A., Petzl-Erler M., Matlashewski G. Ludwig–McGill Study Group 1999; Design and methods of the Ludwig–McGill longitudinal study of the natural history of human papillomavirus infection and cervical neoplasia in Brazil. Rev Panam Salud Publica 6:223–233 [View Article][PubMed]
    [Google Scholar]
  8. Halloran M. E., Struchiner C. J. 1995; Causal inference in infectious diseases. Epidemiology 6:142–151 [View Article][PubMed]
    [Google Scholar]
  9. Hasan U. A., Bates E., Takeshita F., Biliato A., Accardi R., Bouvard V., Mansour M., Vincent I., Gissmann L. other authors 2007; TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16. J Immunol 178:3186–3197[PubMed] [CrossRef]
    [Google Scholar]
  10. Hasimu A., Ge L., Li Q. Z., Zhang R. P., Guo X. 2011; Expressions of Toll-like receptors 3, 4, 7, and 9 in cervical lesions and their correlation with HPV16 infection in Uighur women. Chin J Cancer 30:344–350 [View Article][PubMed]
    [Google Scholar]
  11. Lazarus R., Klimecki W. T., Raby B. A., Vercelli D., Palmer L. J., Kwiatkowski D. J., Silverman E. K., Martinez F., Weiss S. T. 2003; Single-nucleotide polymorphisms in the Toll-like receptor 9 gene (TLR9): frequencies, pairwise linkage disequilibrium, and haplotypes in three U.S. ethnic groups and exploratory case–control disease association studies. Genomics 81:85–91 [View Article][PubMed]
    [Google Scholar]
  12. Lee J. W., Choi J. J., Seo E. S., Kim M. J., Kim W. Y., Choi C. H., Kim T. J., Kim B. G., Song S. Y., Bae D. S. 2007; Increased Toll-like receptor 9 expression in cervical neoplasia. Mol Carcinog 46:941–947 [View Article][PubMed]
    [Google Scholar]
  13. Liu Q., Thorland E. C., Heit J. A., Sommer S. S. 1997; Overlapping PCR for bidirectional PCR amplification of specific alleles: a rapid one-tube method for simultaneously differentiating homozygotes and heterozygotes. Genome Res 7:389–398[PubMed]
    [Google Scholar]
  14. Lu K. C., Yang H. Y., Lin Y. F., Kao S. Y., Lai C. H., Chu C. M., Wu C. C., Su S. L. 2011; The T-1237C polymorphism of the Toll-like receptor-9 gene is associated with chronic kidney disease in a Han Chinese population. Tohoku J Exp Med 225:109–116 [View Article][PubMed]
    [Google Scholar]
  15. Mahmud S. M., Robinson K., Richardson H., Tellier P. P., Ferenczy A. S., Roger M., Coutlee F., Franco E. L. 2007; HLA polymorphisms and cervical human papillomavirus infection in a cohort of Montreal University students. J Infect Dis 196:82–90 [View Article][PubMed]
    [Google Scholar]
  16. Misch E. A., Hawn T. R. 2008; Toll-like receptor polymorphisms and susceptibility to human disease. Clin Sci (Lond) 114:347–360 [View Article][PubMed]
    [Google Scholar]
  17. Netea M. G., Wijmenga C., O’Neill L. A. 2012; Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol 13:535–542 [View Article][PubMed]
    [Google Scholar]
  18. Ng M. T., Van’t Hof R., Crockett J. C., Hope M. E., Berry S., Thomson J., McLean M. H., McColl K. E., El-Omar E. M., Hold G. L. 2010; Increase in NF-κB binding affinity of the variant C allele of the Toll-like receptor 9 −1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease. Infect Immun 78:1345–1352 [View Article][PubMed]
    [Google Scholar]
  19. Novak N., Yu C. F., Bussmann C., Maintz L., Peng W. M., Hart J., Hagemann T., Diaz-Lacava A., Baurecht H. J. other authors 2007; Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy 62:766–772 [View Article][PubMed]
    [Google Scholar]
  20. Pandey S., Mittal B., Srivastava M., Singh S., Srivastava K., Lal P., Mittal R. D. 2011; Evaluation of Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility. Mol Biol Rep 38:4715–4721 [View Article][PubMed]
    [Google Scholar]
  21. Rabachini T., Trottier H., Franco E. L., Villa L. L. 2010; Validation of dot blot hybridization and denaturing high performance liquid chromatography as reliable methods for TP53 codon 72 genotyping in molecular epidemiologic studies. BMC Genet 11:44 [View Article][PubMed]
    [Google Scholar]
  22. Rosa M. I., Moraes M. V., Vuolo F., Petronilho F., Bozzetti M. C., Medeiros L. R., Igansi C. N., Silva F. R., Dal-Pizzol F., Rosa D. D. 2012; Association of interleukin-6 in women with persistence of DNA-HPV: a nested case–control study. Arch Gynecol Obstet 285:143–148 [View Article][PubMed]
    [Google Scholar]
  23. Roszak A., Lianeri M., Sowińska A., Jagodziński P. P. 2012; Involvement of Toll-like receptor 9 polymorphism in cervical cancer development. Mol Biol Rep 39:8425–8430 [View Article][PubMed]
    [Google Scholar]
  24. Schlecht N. F., Kulaga S., Robitaille J., Ferreira S., Santos M., Miyamura R. A., Duarte-Franco E., Rohan T. E., Ferenczy A. other authors 2001; Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA 286:3106–3114 [View Article][PubMed]
    [Google Scholar]
  25. Trottier H., Franco E. L. 2006; The epidemiology of genital human papillomavirus infection. Vaccine 24:Suppl. 1S1–S15 [View Article][PubMed]
    [Google Scholar]
  26. Vandermark E. R., Deluca K. A., Gardner C. R., Marker D. F., Schreiner C. N., Strickland D. A., Wilton K. M., Mondal S., Woodworth C. D. 2012; Human papillomavirus type 16 E6 and E7 proteins alter NF-κB in cultured cervical epithelial cells and inhibition of NF-κB promotes cell growth and immortalization. Virology 425:53–60 [View Article][PubMed]
    [Google Scholar]
  27. Weng Y., Wang Y., Shi Y., Zhou W., Wang H., Wang C. 2011; TLR9 expression and its role in chemosensitivity to DDP in human cervical cancer cells in vitro. J Huazhong Univ Sci Technolog Med Sci 31:550–554 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.052811-0
Loading
/content/journal/jgv/10.1099/vir.0.052811-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error