Revista Mexicana de Periodontología

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>Journals >Revista Mexicana de Periodontología >Year 2017, Issue 2-3

Görnemann CN, Gómez SJR, Fuentes-Lerma MG, Gallegos Arreola MP, Mariaud Schmidt RP
Polymorphism -308 G›A of the gene TNF- α and its role in periodontitis
Rev Mex Periodontol 2017; 8 (2-3)

Language: Español
References: 50
Page: 54-59
PDF: 287.35 Kb.

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Periodontitis is an inflammatory disease characterized by attachment and bone loss because of the interactions between specific subgingival bacteria species and the susceptible host. These interactions lead to the release of inflammatory mediators, such as cytokines, that intervene in the destruction of periodontal tissues in an attempt to control the microorganisms in the gingival sulcus. The tumor necrosis factor alpha (TNF- α) belongs to this group of cytokines; this is why its presence represents a risk factor in the progression and maintenance of periodontal disease. Allelic variations in the cytokine genes and factors that regulate their expression have been found to influence the clinical manifestations and progression of periodontal disease. Several studies have shown that polymorphisms located at the TNF- α gene promoter have a significant effect on its transcriptional activity. Although the -308 polymorphism is located at the promotor of the mentioned gene, and there is a change of alleles (G›A), the functional changes caused by the gene are not clear. Several studies have been made in different populations across the world, resulting in controversial results regarding the association of the -308 polymorphism and periodontal disease. TNF- α polymorphisms can appear with alternative allelic patterns in different populations. The use of molecular techniques and their diagnostic application in dentistry, particularly in periodontal disease, has made it possible to learn about this disease and its evolution. Exploring these tools will allow us to elucidate if there is an association between the -308G›A polymorphism of the TNF- α gene and the progression and severity of periodontal disease in our population.

Key words: Periodontitis, TNF- α, -308 G›A polymorphism.


  1. Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000. 1997; 14: 33-53.

  2. Kornman KS. Mapping the pathogenesis of periodontitis: a new look. J Periodontol. 2008; 79 (8 Suppl): 1560-1568.

  3. Newman MG, Takei HH, Carranza FA. Periodontología clínica. 12.ª ed. Canadá: Elsevier; 2015.

  4. Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 2003; 74 (3): 391-401.

  5. Zucali JR, Elfenbein GJ, Barth KC, Dinarello CA. Effects of human interleukin 1 and human tumor necrosis factor on human T lymphocyte colony formation. J Clin Invest. 1987; 80 (3): 772-777.

  6. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000. 1997; 14: 9-11.

  7. Graves DT. The potential role of chemokines and inflammatory cytokines in periodontal disease progression. Clin Infect Dis. 1999; 28 (3): 482-490.

  8. Silva MJ, Sousa LM, Lara VP, Cardoso FP, Junior GM, Totola AH et al. The role of iNOS and PHOX in periapical bone resorption. J Dent Res. 2011; 90 (4): 495-500.

  9. Tai H, Endo M, Shimada Y, Gou E, Orima K, Kobayashi T et al. Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese. J Clin Periodontol. 2002; 29 (10): 882-888.

  10. Yang W, Jia Y, Wu H. Four tumor necrosis factor alpha genes polymorphisms and periodontitis risk in a Chinese population. Hum Immunol. 2013; 74 (12): 1684-1687.

  11. Taubman MA, Kawai T, Han X. The new concept of periodontal disease pathogenesis requires new and novel therapeutic strategies. J Clin Periodontol. 2007; 34 (5): 367-369.

  12. Kanakdande V, Patil KP, Nayyar AS. Comparative evaluation of clinical, hematological and systemic inflammatory markers in smokers and non-smokers with chronic periodontitis. Contemp Clin Dent. 2015; 6 (3): 348-357.

  13. Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol. 2005; 32 (6): 57-71.

  14. Ohlrich EJ, Cullinan MP, Seymour GJ. The immunopathogenesis of periodontal disease. Aust Dent J. 2009; 54 (Suppl 1): S2-10.

  15. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003; 423 (6937): 337-342.

  16. Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008; 79 (8 Suppl): 1569-1576.

  17. Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest. 2005; 115 (2): 282-290.

  18. Loos BG, John RP, Laine ML. Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol. 2005; 32 (Suppl 6): 159-179.

  19. Brenner DA, O’Hara M, Angel P, Chojkier M, Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989; 337 (6208): 661-663.

  20. Graves DT, Oskoui M, Volejnikova S, Naguib G, Cai S, Desta T et al. Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection. J Dent Res. 2001; 80 (10): 1875-1879.

  21. Correa FO, Gonçalves G, Figueredo CM, Bastos AS, Gustafsson A, Orrico SR. Effect of periodontal treatment on metabolic control, systemic inflammation and cytokines in patients with type 2 diabetes. J Clin Periodontol. 2010; 37 (1): 53-58.

  22. Sexton WM, Lin Y, Kryscio RJ, Dawson III DR, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol. 2011; 38 (5): 434-441.

  23. Kejriwal S, Bhandary R, Thomas B, Kumari S. Estimation of levels of salivary mucin, amylase and total protein in gingivitis and chronic periodontitis patients. J Clin Diagn Res. 2014; 8 (10): ZC56-60.

  24. Pennica, D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA et al. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984; 312: 724-729.

  25. Nedwin GE, Svedersky LP, Bringman TS, Palladino MA Jr, Goeddel DV. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985; 135 (4): 2492-2497.

  26. Herrmann SM, Ricard S, Nicaud V, Mallet C, Arveiler D, Evans A et al. Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity. Eur J Clin Invest. 1998; 28 (1): 59-66.

  27. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol. 1997; 34 (5): 391-399.

  28. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997; 94 (7): 3195-3199.

  29. Elahi MM, Asotra K, Matata BM, Mastana SS. Tumor necrosis factor alpha -308 gene locus promoter polymorphism: An analysis of association with health and disease. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 2009; 1792 (3): 163-172.

  30. Chen D, Liu JL, Liu Y, Zhu J, Wang SW. Lack of an association between -308G>A polymorphism of the TNF-alpha gene and liver cirrhosis risk based on a meta-analysis. Genet Mol Res. 2011; 10: 2765-2774.

  31. Matthews N. Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action. Br J Cancer. 1983; 48 (3): 405-410.

  32. Skoog T, van’t Hooft FM, Kallin B, Jovinge S, Boquist S, Nilsson J et al. A common functional polymorphism (C>A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet. 1999; 8: 1443-1449.

  33. Karthikeyan R, Peeran SW, Murugan M, Awidat K, Basheer O, Al Mugrabi MH. Single nucleotide polymorphisms and periodontitis. Dent Med Res. 2014; 2 (1): 3-7.

  34. Khosropanah H, Sarvestani EK, Mahmoodi A, Golshah M. Association of IL-8 (-251 A/T) gene polymorphism with clinical parameters and chronic periodontitis. J Dent (Tehran). 2013; 10 (4): 312-318.

  35. Ni XB, Jia C, Yu HD, Li YQ, Zeng XT, Leng WD. Comprehensive analysis of interleukin-8 gene polymorphisms and periodontitis susceptibility. Oncotarget. 2017; 8 (30): 48996-49004.

  36. Cereda C, Cova E, Diamanti L, Ceroni M, Gagliardi S. The role of TNF-alpha in ALS: New hypotheses for future therapeutic approaches. Amyotrophic-lateral-sclerosis. In Tech. 2012: 413-435.

  37. Guadagni F, Ferroni P, Palmirotta R, Portarena I, Formica V, Roselli M. Review TNF/VEGF cross-talk in chronic inflammation related cancer initiation and progression: an early target in anticancer therapeutic strategy. In Vivo. 2007; 21 (2): 147-161.

  38. Qing H, Guo-Guang L, Ying-Chao L, LeQian, Bo-Dong L. The tumor necrosis factor α -308 and -238 polymorphisms and risk of hepatocellular carcinoma for Asian populations: a meta-analysis. Curr Ther Res Clin Exp. 2014; (76): 70-75.

  39. Da Costa TA, Silva MJ, Alves PM, Chica JE, Barcelos EZ, Giani MA et al. Inflammation biomarkers of advanced disease in nongingival tissues of chronic periodontitis patients. Mediators Inflamm. 2015; 2015: 983782.

  40. Pociot F, D’Alfonso S, Compasso S, Scorza R, Richiardi PM. Functional analysis of a new polymorphism in the human TNF-alpha gene promoter. Scand J Immunol. 1995; 42 (4): 501-504.

  41. Özer Yücel Ö, Berker E, Mesci L, Eratalay K, Tepe E, Tezcan İ. Analysis of TNF-α (-308) polymorphism and gingival crevicular fluid TNF-α levels in aggressive and chronic periodontitis: a preliminary report. Cytokine. 2015; 72 (2): 173-177.

  42. Song GG, Choi SJ, Ji JD, Lee JH. Association between tumor necrosis factor-a promoter -308 A/G,-238 A/G, interleukin-6 -174 G/C and -572 G/C polymorphisms and periodontal disease: a meta-analysis. Mol Biol Rep. 2013; 40: 5191-5203.

  43. D’Aiuto F, Parkar M, Brett PM, Ready D, Tonetti MS. Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections. Cytokine. 2004; 28 (1): 29-34.

  44. Galbraith GM, Hendley TM, Sanders JJ, Palesch Y, Pandey JP. Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis. J Clin Periodontol. 1999; 26 (11): 705-709.

  45. Ding C, Ji X, Chen X, Xu Y, Zhong L. TNF-α gene promoter polymorphisms contribute to periodontitis susceptibility: evidence from 46 studies. J Clin Periodontol. 2014; 41: 748-759.

  46. Wang S, Lewis CM Jr., Jakobsson M, Ramachandran S, Ray N, Bedoya G et al. Genetic variation and population structure in Native Americans. PLoS Genet. 2007; 3 (11): e185.

  47. Acuña AV, Flores DT, Kruit JK, Villareal MT, Arellano O, Hünemeier T et al. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans. Hum Mol Genet. 2010; 19 (14): 2877-2885.

  48. Williams AL, Jacobs SB, Moreno MH, Huerta CA, Churchhouse C, Márquez LC et al. Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature. 2014; 506: 97-101.

  49. Vázquez-Huerta DI, Alvarez-Rodríguez BA, Topete-Reyes JF, Muñoz-Valle JF, Parra-Michel R, Fuentes-Ramírez F et al. Tumor necrosis factor alpha -238 G/A and -308 G/A polymorphisms and soluble TNF-α levels in chronic kidney disease: correlation with clinical variables. Int J Clin Exp Med. 2014; 7 (8): 2111-2119.

  50. Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV et al. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science. 2014; 344 (6189): 1280-1285.

>Journals >Revista Mexicana de Periodontología >Year 2017, Issue 2-3

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