Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 6, November-December, p. 1059–1070

doi: 10.17219/acem/47394

Publication type: original article

Language: English

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Polymorphisms of Toll-Like Receptor 4 as a Risk Factor for Periodontitis: Meta-Analysis

Dariusz Chrzęszczyk1,A,B,D,E,F, Tomasz Konopka1,A,C,D,E,F, Marek Ziętek1,A,D,E,F

1 Department of Periodontology, Wroclaw Medical University, Poland

Abstract

Background. Toll-like receptors play an important role in the recognition of periopathogens. There are widely known polymorphisms of these receptors that may alter host susceptibility to periodontitis.
Objectives. Evaluating the association of TLR4 polymorphisms (Asp299 and Thr399Ile) with the occurrence of periodontitis and its two clinical types: chronic (CP) and aggressive (AgP) among Caucasians.
Material and Methods. A review of 4 electronic databases was made to identify studies that match the inclusion criteria for the meta-analysis and were published up to December 31, 2013.
Results. Fifteen studies met the inclusion criteria. For Asp299Gly polymorphism 1621 patients with periodontitis (1148 with CP and 473 with AgP) and 1755 individuals without clinical signs of periodontitis were included in the meta-analysis. The occurrence of polymorphism The399Ile was evaluated among 1522 patients with periodontitis (1017 with CP and 505 with AgP) and 1461 subjects in the control group. The pooled OR with a random effects model for the Asp299Gly and chronic periodontitis was 1.35 (95% CI: 1.02–1.8, p = 0.038), indicating a possible association between this polymorphism and CP. Other published meta-analyzes showed no significant association between single nucleotide polymorphisms of TLR4 and periodontitis nor its clinical types. No publication bias was reported.
Conclusion. Our meta-analysis showed statistically significant association between TLR4 Asp299Gly allele and increased susceptibility to chronic periodontitis.

Key words

toll-like receptor, polymorphisms, periodontitis, meta-analysis

References (39)

  1. Laine ML, Crielaard W, Loos BG: Genetic susceptibility to periodontitis. Periodontol 2000 2012, 58, 37–68.
  2. Laine ML, Loos BG, Crielaard W: Gene polymorphisms in chronic periodontitis. Int J Dent 2010, ID 324719.
  3. Szparecki G, Czerkies M, Miskiewicz A: A new approach for genetic factors influencing periodontitis. Dent Med Probl 2013, 50, 145–151.
  4. Kornman KS, Crane A, Wang HY, di Giovine FS, Newman MG, Pirk FW, Wilson TG, Higginbottom FL, Duff GW: The interleukin-1 genotype as a severity factor in adult periodontitis disease. J Clin Periodontol 1997, 24, 72–77.
  5. Nikolopoulos GK, Dimou NL, Hamodrakas SJ, Bagos PG: Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4148 cases and 4590 controls. J Clin Periodontol 2008, 35, 754–767.
  6. Takeda K, Akira S: Toll-like receptors in innate immunity. Int Immunol 2005, 17, 1–14.
  7. Drexler SK, Foxwell BM: The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol 2010, 42, 506–518.
  8. Uematsu S, Akira S: Toll-like receptors (TLRs) and their ligands. Handb Exp Pharmacol 2008, 183, 1–20.
  9. Kikkert R, Laine ML, Aarden LA, van Winkelhoff AJ: Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria. Oral Microbiol Immunol 2007, 22, 145–151.
  10. Mayank Ha, Veenu Madaan H: Tool-like receptors and their dual role in periodontitis: a review. J Oral Sci 2011, 53, 263–271.
  11. Noreen M, Shah MAA, Mall SM, Choudhary S, Hussain T, Ahmed I, Jalil SF, Raza MI: TLR4 polymorphisms and disease susceptibility. Inflamm Res 2012, 61, 177–188.
  12. Zhu G, Li C, Cao Z, Corbet EF, Jin L: Toll-like receptors 2 and 4 gene polymorphisms in a Chinese population with periodontitis. Quintes Int 2008, 39, 217–226.
  13. Ferwerda B, McCall MB, Verheijen K, Kullberg B-J, Jam van der Ven AJ, Van der Meer JW, Netea MG: Functional consequences of toll-like receptor 4 polymorphisms. Mol Med 2008, 14, 346–352.
  14. Ziakas PD, Prodromou ML, El Khoury J, Zintzaras E, Mylonakis E: The role of TLR4 896A > G and 1196 C > T in susceptibility to infections: a review and meta-analysis of genetic association studies. PLoS ONE 2013, 8, 11, e81047.
  15. Beklen A, Hukkanen M, Richardson R, Konttinen YT: Immunohistochemical localization of Toll-like receptors 1–10 in periodontitis. Oral Microbiol Immunol 2008, 23, 425–431.
  16. Kinane DF, Shiba H, Stathopoulou PG, Zhao H, Lappin DF, Singh A, Eskan MA, Beckers S, Waigel S, Alpert B, Knudsen TB: Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile are hypo-responsive to Porphyromonas gingivalis. Gen Immun 2006, 7, 190–200.
  17. Moher D, Liberati A, Tezlaff J, Altman DG: PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PloS Med 2009, 6, e10000097.
  18. 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 2004, 135, 330–335.
  19. Schröder NW, Meister D, Wolff V, Christan C, Kaner D, Haban V, Purucker P, Hermann C, Moter A, Göbel UB, Schumann RR: Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene. Gen Immun 2005, 6, 448–451.
  20. Brett PM, Zygogianni P, Griffiths GS, Tomaz M, Parkar M, D’Aiuto F, Tonetti M: Functional gene polymorphisms in aggressive and chronic periodontitis. J Dent Res 2005, 84, 1149–1153.
  21. Laine ML, Morré SA, Murillo LS, van Winkelhoff AJ, Peña AS: CD14 and TLR4 gene polymorphisms in adult periodontitis. J Dent Res 2005, 84, 1042–1046.
  22. James JA, Poulton KV, Haworth SE, Payne D, McKay IJ, Clarke FM, Hughes FJ, Linden GJ: Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis. J Clin Periodontol 2007, 34, 111–117.
  23. Berdeli A, Emingil G, Saygan BH, 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 2007, 34, 551–557.
  24. Emingil G, Berdeli A, Baylas H, Saygan BH, Gürkan A, Köse T, Atilla G: Toll-like receptor 2 and 4 gene polymorphisms in generalized aggressive periodontitis. J Periodontol 2007, 78, 1968–1977.
  25. Holla I, 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 Periodont Res 2007, 42, 340–344.
  26. Reismann P, Lichy C, Rudofsky G, Nawroth P, Staehle H, Bierhaus A, Dorfer CE: TLR4-polymorphisms and the risk of chronic periodontitis. Perio 2007, 4, 41–45.
  27. Tervonen T, Raunio T, Knuuttila M, Karttunen R: Polymorphisms in the CD14 and IL-6 genes associated with periodontal disease. J Clin Periodontol 2007, 34, 377–383.
  28. Schulz S, Zissler N, Altermann W, Klapproth J, Zimmermann U, Gläser C, Schaller HG, Reichert S: Impact of genetic variants of CD14 and TLR4 on subgingival periodontopathogens. Int J Immunogenet 2008, 35, 457–464.
  29. Noack B, Görgens H, Lorenz K, Ziegler A, Hoffmann T, Schackert HK: TLR4 and IL-18 gene variants in aggressive periodontitis. J Clin Periodontol 2008, 35, 1020–1026.
  30. Noack B, Görgens H, Lorenz K, Schackert HK, Hoffmann T: TLR4 and IL-18 gene variants in chronic periodontitis: impact on disease susceptibility and severity. Immunol Invest 2009, 38, 297–310.
  31. Sahingur SE, Xia XJ, Gunsolley J, Schenkein HA, Genco RJ, De Nardin E: Single nucleotide polymorphisms of pattern recognition receptors and chronic periodontitis. J Periodont Res 2011, 46, 184–192.
  32. Chrzęszczyk D: The role of receptor TLR-2 and TLR-4 in the pathogenesis of periodontitis. Doctoral thesis, Wroclaw Medical University 2013.
  33. Ozturk A, Vieira AR: TLR4 as a risk factor for periodontal disease: a reappraisal. J Clin Periodontol 2009, 36, 279–286.
  34. Song GG, Kim J-H, Lee YH: Tool-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis. Mol Biol Rep 2013, 40, 5129–5141.
  35. Garlet GP, Trombone APF, Menezes R, Letra A, Repeke CE, Vieira AE, Martins W, Teixeira das Neves LT, Campanelli AP, Ferreira dos Santos CF, Vieira AR: The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies – a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition. J Clin Periodontal 2012, 39, 323–332.
  36. Imamura Y, Fujigaki Y, Oomori Y, Kuno T, Ota N, Wang PL: Polymorphism of genes encoding toll-like receptors and inflammatory cytokines in periodontal disease in the Japanese population. J Int Acad Periodontol 2008, 10, 95–102.
  37. 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 Periodont Res 2007, 42, 541–545.
  38. Reddy BH, Jayakumar ND, Akula SR, Sharma R, Kaarthikeyan G, Sankari: Analysis of association between TLR-4 Asp299Gly and Thr399Ile gene polymorphisms and chronic periodontitis in a sample of south Indian population. J Indian Soc Periodontol 2011, 15, 366–370.
  39. Laine ML, Moustakis V, Koumakis L, Potamias G, Loos BG: Modeling susceptibility to periodontitis. J Dent Res 2013, 92, 45–50.
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