Variability in Toll-like Receptor Genes and Their Relation to Occurrence of Periodontal Pathogens in Chronic Periodontitis
Authors:
L. Izakovičová Hollá 1,2; B. Hrdličková 1; J. Vokurka 2; P. Augustín 2; A. Fassmann 2; J. Vaněk 2
Authors place of work:
Ústav patologické fyziologie LF MU, Brno
1; Stomatologická klinika LF MU a FN u sv. Anny, Brno
2
Published in the journal:
Česká stomatologie / Praktické zubní lékařství, ročník 111, 2011, 5, s. 107-116
Category:
Original Article – Clinical Analytical Study
Summary
Introduction:
Toll-like receptors (TLRs) belong to the pattern recognition receptor family of signal molecules that recognize heterogeneous antigens. The aim of this study was to analyze polymorphisms in the TLR genes and their association with the presence of selected periodontal pathogens and clinical manifestation of chronic periodontitis (CP).
Methods:
Two polymorphisms in TLR-2, two SNPs in TLR-4 and three variants in TLR-9 genes were studied in 216 patients with CP and 184 unrelated controls. All polymorphisms were detected using the PCR-RFLP methods. The subgingival presence of 7 selected periodontal pathogens was investigated by the VariOr®Dento test.
Results:
No significant differences were found in frequencies of alleles or genotypes of all polymorphisms in the TLR-2, TLR-4 and TLR-9 genes between patients with CP and controls. However, in a complex analysis, significant differences in frequencies of TLR-9 haplotypes were determined between both groups. Haplotype TLR-9 “TTA” was significantly more frequent (9.8% vs. 2.8%, p < 0.00005) and haplotype “TTG” less frequent (33.7% vs. 41.3%, p = 0.03) in patients with CP in comparison with controls.
We did not find significant differences in frequencies of TLR-2 and TLR-4 haplotypes between both groups. Comparison of the occurrence of the selected periodontal pathogens confirmed significant differences in frequencies of P. gingivalis, T. forsythensis, P. micros, P. intermedia. (p < 0.01) and marginal differences in the occurrence of T. denticola and F. nucleatum (p < 0.05) between the group of patients and controls. In contrast, no significant difference between both groups was found for A. actinomycetemcomitans. No significant associations between CP, periodontal pathogens and TLR-2 or TLR-9 polymorphisms was observed in any group; however, we found marginal correlation of both TLR-4 variants with the occurrence of P. gingivalis (p = 0.05).
Conclusions:
In conclusion, these findings suggest that TLR-9 haplotypes may be associated with susceptibility to chronic periodontitis and indicate a possible interaction between the occurrence of some bacteria in the subgingival plaque and polymorphisms in the TLR-4 gene; this finding is in agreement with multifactorial etiology of this disease.
Key words:
periodontitis – gene – polymorphism – bacteria – association – haplotype
Zdroje
1. Arancibia, S. A., Beltran, C. J., Aguirre, I. M., Silva, P., Peralta, A. L., Malinarich, F., Hermoso, M. A.: Toll-like receptors are key participants in innate immune response. Biol. Res., roč. 40, 2007, č. 2, s. 97–112.
2. Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., Schwartz, D. A.: TLR4 mutations are associated with endotoxin hyporresponsiveness in humans. Nat. Genet., roč. 25, 2000, č. 2, s. 187–191.
3. Armitage, G. C.: Development of a classification system for periodontal diseases and conditions. Ann. Periodontol., roč. 4, 1999, č. 1, s. 1–6.
4. Bauer, S., Kirschning, C. J., Hacker, H., Redecke, V., Hausmann, S., Akira, S., Wagner, H., Lipford, G. B.: Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc. Natl. Acad. Sci. USA, roč. 98, 2001, č. 16, s. 9237–9242.
5. Berdeli, A., Celik, H.A., Ozyürek, R., Dogrusoz, B., Aydin, H.H.: TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children. J. Mol. Med., roč. 83, 2005, č. 7, s. 535–541.
6. Berdeli, A., Emingil, G., Han Saygan, B., Gürkan, A., Atilla, G., Köse, T., Baylas, H.: TLR2 Arg753Gly, TLR4 Asp299Gly and Thr399Ile gene polymorphisms are not associated with chronic periodontitis in a Turkish population. J. Clin. Periodontol, roč. 34, 2007, č. 7, s. 551–557.
7. Berghöfer, B., Frommer, T., König, I. R., Ziegler, A., Chakraborty, T., Bein, G., Hackstein, H.: Common human Toll-like receptor 9 polymorphisms and haplotypes: association with atopy and functional relevance. Clin. Exp. Allergy, roč. 35, 2005, č. 9, s. 1147–1154.
8. Borrell, L. N., Papapanou, P. N.: Analytical epidemiology of periodontitis. J. Clin. Periodontol., roč. 32, 2005, Suppl. č. 1, s. 132–158.
9. Brett, P. M., Zygogianni, P., Griffiths, G. S., Tomaz, M., Parkar, M., D’Aiuto, F., Tonetti, M.: Functional gene polymorphisms in aggressive and chronic periodontitis. J. Dent. Res., roč. 84, 2005, č. 12, s. 1149–1153.
10. Coban, C., Ishii, K. J., Kawai, T., Hemmi, H., Sato, S., Uematsu, S., Yamamoto, M., Takeuchi, O., Itagaki, S., Kumar, N., Horii, T., Akira, S.: Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozin. J. Exp. Med., roč. 201, 2005, č. 1, s. 19–25.
11. Du, X., Poltorak, A., Wei, Y., Beutler, B.: Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur. Cytokine Netw., roč. 11, 2000, č. 3, s. 362–371.
12. Emingil, G., Berdeli, A., Baylas, H., Saygan, B. H., Gürkan, A., Köse, T., Atilla, G.: Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive periodontitis. J. Periodontol., roč. 78, 2007, č. 10, s. 1968–1977.
13. Folwaczny, M., Glas, J., Török, H.P., Limbersky, O., Folwaczny, C.: Toll-like receptor (TLR) 2 and 4 mutations in periodontal disease. Clin. Exp. Immunol., roč. 135, 2004, č. 2, s. 330–335.
14. Fukusaki, T., Ohara, N., Hara, Y., Yoshimura, A., Yoshiura, K.: Evidence for association between a Toll-like receptor 4 gene polymorphism and moderate/severe periodontitis in the Japanese population. J. Periodontal Res., roč. 42, 2007, č. 6, s. 541–545.
15. Haffajee, A. D., Socransky, S. S.: Microbial etiological agents of destructive periodontal disease. Periodonto1. 2000, roč. 5, 1994, č. 1, s. 78–111.
16. Hamann, L., Hamprecht, A., Tomka, A., Schumann, R. R.: Rapid and inexpensive real-time PCR for genotyping functional polymorphisms within the Toll-like receptor -2, -4, and -9 genes. J. Immunol. Methods, roč. 285, 2004, č. 2, s. 281–291.
17. Hamann, L., Glaeser, Ch., Haprecht, A., Gross, M., Gomma, A., Schumann, R.R.: Toll-like receptor (TLR)-9 promotor polymorphisms and atherosclerosis. Clin. Chim. Acta, roč. 364, 2006, č. 1–2, s. 303–307.
18. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., Akira, S.: A Toll-like receptor recognizes bacterial DNA. Nature, roč. 408, 2000, č. 6813, s. 740–745.
19. Imamura, Y., Fujigaki, Y., Oomori, Y., Kuno, T., Ota, N., Wang, P.L.: Polymorphism of genes encoding toll-like receptors and inflammatory cytokines in periodontal disease in the Japanese population. J. Int. Acad. Periodontol., roč. 10, 2008, č. 3, s. 95–102.
20. Izakovicova Holla, L., Buckova, D., Fassmann, A., Roubalikova, L., Vanek, J.: Lack of association between chronic periodontitis and the Toll-like receptor 4 gene polymorphisms in a Czech population. J. Periodontal. Res., roč. 42, 2007, č. 4, s. 340–344.
21. Izakovicova Holla, L., Vokurka, J., Hrdlickova, B., Augustin, P., Fassmann, A.: Association of TLR9 haplotypes with chronic periodontitis in Czech population. J. Clin. Periodontol., roč. 37, 2010, č. 2, s. 152–159.
22. James, J. A., Poulton, K. V., Haworth, S. E., Payne, D., McKay, I. J., Clarke, F. M., Hughes, F. J., Linden, G. J.: Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis. J. Clin. Periodontol., roč. 34, 2007, č. 2, s. 111–117.
23. Kajita, K., Honda, T., Amanuma, R., Domon, H., Okui, T., Ito, H., Yoshie, H., Tabeta, K., Nakajima, T., Yamazaki, K.: Quantitative messenger RNA expression of Toll-like receptors and interferon-alpha1 in gingivitis and periodontitis. Oral Microbiol. Immunol., roč. 22, 2007, č. 6, s. 398–402.
24. Kikuchi, K., Lian, Z. X., Kimura, Y., Selmi, C., Yang, G. X., Gordon, S. C., Invernizzi, P., Podda, M., Coppel, R. L., Ansari, A. A., Ikehara, S., Miyakawa, H., Gershwin, M. E.: Genetic polymorphisms of toll-like receptor 9 influence the immune response to CpG and contribute to hyper-IgM in primary biliary cirrhosis. J. Autoimmun., roč. 24, 2005, č. 4, s. 347–352.
25. Laine, M. L., Morré, S. A., Murillo, L. S., van Winkelhoff, A. J., Pena, A. S.: CD14 and TLR4 gene polymorphisms in adult periodontitis. J. Dent. Res., roč. 84, 2005, č. 11, s. 1042–1046.
26. Laine, M. L., Loos, B. G., Crielaard, W.: Gene Polymorphisms in Chronic Periodontitis. Int. J. Dent., 2010, 2010:324719. Epub 2010 Feb 9.
27. Lazarus, R., Klimecki, W. T., Raby, B. A., Vercelli, D., Palmer, L. J., Kwiatkowski, D. J., Silverman, E. K., Martinez, F., Weiss, S. T.: 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, roč. 81, 2003, č. 1, s. 85–91.
28. Lorenz, E., Mira, J. P., Cornish, K. L., Arbour, N. C., Schwartz, D. A.: A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect. Immun., roč. 68, 2000, č. 11, s. 6398–6401.
29. Lorenz, E., Hallman, M., Marttila, R., Haataja, R., Schwartz, D. A.: Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr. Res., roč. 52, 2002, č. 3, s. 373–376.
30. Mahanonda, R., Pichyangkul, S.: Toll-like receptors and their role in periodontal health and disease. Periodontol., 2000, roč. 43, 2007, č. 1, s. 41–55.
31. Martin, M., Katz, J., Vogel, S. N., Michalek, S. M.: Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. J. Immunol., roč. 167, 2001, č. 9, s. 5278–5285.
32. Mühlemann, H. R., Mazor, Z. S.: Röntgendiagnostik. Schweizerische Monatsschrift für Zahnheilkunde, roč. 65, 1955, s. 1005–1013.
33. Nibali, L., Ready, D. R., Parkar, M., Brett, P. M., Wilson, L., Tonetti, M. S., Griffiths, G. S.: Gene polymorphisms and the prevalence of key periodontal pathogens. J. Dent. Res., roč. 86, 2007, č. 5, s. 416–420.
34. Nieters, A., Beckmann, L., Deeg, E., Becker, N.: Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun., roč. 7, 2006, č. 8, s. 615–624.
35. Noack, B., Görgens, H., Lorenz, K., Ziegler, A., Hoffmann, T., Schackert, H. K.: TLR4 and IL-18 gene variants in aggressive periodontitis. J. Clin. Periodontol., roč. 35, 2008, č. 12, s. 1020–1026.
36. Novak, N., Yu, C. F., Bussmann, C., Maintz, L., Peng, W. M., Hart, J., Hagemann, T., Diaz-Lacava, A., Baurecht, H. J., Klopp, N., Wagenpfeil, S., Behrendt, H., Bieber, T., Ring, J., Illig, T., Weidinger, S.: Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy, roč. 62, 2007, č. 7, s. 766–772.
37. Ogus, A. C., Yoldas, B., Ozdemir, T., Uguz, A., Olcen, S., Keser, I., Coskun, M., Cilli, A., Yegin, O.: The Arg753Gln polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur. Respir. J., roč. 23, 2004, č. 2, s. 219–223.
38. Ozturk, A., Vieira, A. R.: TLR4 as a risk factor for periodontal disease: a reappraisal. J. Clin. Periodontol., roč. 36, 2009, č. 4, s. 279–286.
39. Sarah, S. M., Tamilselvan, S., Kamatchiammal, S., Suresh, R.: Expression of Toll-like receptors 2 and 4 in gingivitis and chronic periodontitis. Indian J. Dent. Res., roč. 17, 2006, č. 3, s. 114–116.
40. Schröder, N. W. J., Hermann, C., Hamann, L., Göbel, U. B., Schumann, T. H. R.: High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J. Mol. Med, roč. 81, 2003, č. 6, s. 368–372.
41. Schröder, N. W., Meister, D., Wolff, V., Christan, C., Kaner, D., Haban, V., Purucker, P., Hermann, C., Moter, A., Göbel, U. B., Schumann, R. R.: Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene. Genes Immun., roč. 6, 2005, č. 5, s. 448–451.
42. Schulz, S., Zissler, N., Altermann, W., Klapproth, J., Zimmermann, U., Gläser, C., Schaller, H. G., Reichert, S.: Impact of genetic variants of CD14 and TLR4 on subgingival periodontopathogens. Int. J. Immunogenet., roč. 35, 2008, č. 6, s. 457–464.
43. Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C., Kent, R. L. Jr.: Microbial complexes in subgingival plaque. J. Clin. Periodontol., roč. 25, 1998, č. 2, s. 134–144.
44. Stephens, M., Smith, N. J., Donnelly, P.: A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet., roč. 68, 2001, č. 4, s. 978–989.
45. Stephens, M., Donnelly, P.: A comparison of Bayesian methods for haplotype reconstruction. Am. J. Hum. Genet., roč. 73, 2003, č. 5, s. 1162–1169.
46. Sutherland, A. M., Walley, K. R., Russell, J. A.: Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults. Crit. Care Med., roč. 33, 2005, č. 3, s. 638–644.
47. Takeda, K., Akira, S.: Toll-like receptors in innate immunity. Int. Immunol., roč. 17, 2005, č. 1, s. 1–14.
48. Tao, K., Fujii, M., Tsukumo, S., Maekawa, Y., Kishihara, K., Kimoto, Y., Horiuchi, T., Hisaeda, H., Akira, S., Kagami, S., Yasutomo, K.: Genetic variations of toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population. Ann. Rheum.Dis., roč. 66, 2007, č. 7, s. 905–909.
49. Tervonen, T., Raunio, T., Knuuttila, M., Karttunen, R.: Polymorphisms in the CD14 and IL-6 genes associated with periodontal disease. J. Clin. Periodontol., roč. 34, 2007, č. 5, s. 377–383.
50. Xu, C. H. J., Zhang, W. H., Pan, H. F., Li, X. P., Xu, J. H., Ye, D. Q.: Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic lupus erythematosus among Chinese. Mol. Biol. Rep., roč. 36, 2009, č. 8, s. 2245–2248.
51. Yoshie, H., Kobayashi, T., Tai, H., Galicia, J. C.: The role of genetic polymorphisms in periodontitis. Periodontol., 2000, roč. 43, 2007, č. 1, s. 102–132.
52. Zhu, G., Li, C., Cao, Z., Corbet, E. F., Jin, L.: Toll-like receptors 2 and 4 gene polymorphisms in a Chinese population with periodontitis. Quintessence Int., roč. 39, 2008, č. 3, s. 217–226.
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