Articles
 

Gene Polymorphisms of TNF-α and IL-1β Are Not Associated with Generalized Aggressive Periodontitis in an Iranian Subpopulation

Abstract

Cytokines play a part in pathogenesis of periodontitis via inflammation phenomenon. Aggressive periodontitis (AgP) is a multifactorial disease resulting in rapid tooth loss due to severe destruction of tooth supporting apparatus. Recently, researchers have focused on genetic susceptibility of periodontitis through investigating the gene variations of cytokines and other components of immune response. In this study we analyzed single nucleotide polymorphism (SNP) of two cytokines in association with AgP in an Iranian-Khorasani population; Interleukin-1 beta (IL-1β) +3954 C/T and Tumor Necrosis Factor alpha (TNF- α) -308 G/A.
From arm vein of patients (n=58) and periodontally healthy individuals (n=60) blood sample was obtained and the DNA was extracted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) procedure was performed to recognize the SNPs. X2 test was used to determine the statistically significant differences between the two groups.
The frequency of genotypes and alleles had no significant differences between patients and control  groups. The  distributions  were as  follows. IL-1β +3954:  CT, CC and  TT genotypes in patients were 39.6%, 60.4% and 0.0% and in controls were 41.7%, 50% and 8.3%, respectively. TNF-α -308: GA, GG and AA genotypes in patients were 44.8%, 41.4% and 13.8% and in controls were 46.7%, 50% and 3.3%, respectively.
This investigation do not substantiates the role of IL-1β +3954 and TNF-α -308 polymorphisms, separately, as risk determinants for AgP in Iranian population. Further research based on all components of immune response, is needed to corroborate the genetic susceptibility of AgP.

1. Picolos DK, Lerche-Sehm J, Abron A, Fine JB, Papapanou PN. Infection patterns in chronic and aggressive Periodontitis. J Clin Periodontol 2005; 32(10):1055–61.
2. Gera I, Vári M, Fogorv Sz. Genetic background of periodontitis. Part I. Basic principles and syndromes with mendelian inheritance. Review of literature 2009;102(3):87-99.
3. McFarlane CG, Reynolds JJ, Meikle MC. The release of interleukin-1 beta, tumor necrosis factor-alpha and interferon-gamma by cultured peripheral blood mononuclear cells from patients with periodontitis. J Periodont Res 1990; 25(4):207-14.
4. Bastos MF, Lima JA, Vieira PM, Mestnik MJ, Faveri M, Duarte PM. TNF- alpha and IL-4 levels in generalized aggressive periodontitis subjects. Oral Dis 2009;15(1):82-7.
5. Teles RP, Sakellari D, Konstantinidis A, Socransky SS, Haffajee AD. Application of the checkerboard immunoblotting technique to the quantification of host biomarkers in gingival crevicular fluid. J Periodontol2009; 80(3):447-56.
6. 6- Iwasaki LR, Chandler JR, Marx DB, Pandey JP, Nickel JC. IL-1 gene polymorphisms, secretion in gingival crevicular fluid, and speed of human orthodontic tooth movement. Orthod Craniofac Res 2009; 12(2):129-40.
7. 7- Steinsvoll S, Halstensen TS, Schenck K. Extensive expression of TGF-β, in chronically-inflammed periodontal tissue. J Clin Periodontol 1999; 26(6):366-73.
8. Takahashi K, Takigawa M, Takashiba S, Nagai A, Miyamoto M, Kurihara H, et al. Role of cytokine in the induction of adhesion molecules on cultured human gingival fibroblasts. J Periodontol 1994; 65(3): 230-5.
9. Sorensen LK, Havemose-Poulsen A, Bendtzen K, Holmstrup P. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors. J Periodontol 2009; 80(2); 282-9.
10. Langdahl BL, Lokke E, Carstens M, Stenkjaer LL, Eriksen EF. Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1-receptor antagonist gene but not with polymorphisms in the interleukin-1 beta gene. J Bone Miner Res 2000;15(3):402-14.
11. Mariette X. Anti-cytokines in the treatment of inflammation. Rev Prat 2003; 53(5):507-11.
12. Wilson AG, Symons JA, McDowell TL, McDevitt HO,Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter ontranscriptional activation. Proc Natl Acad Sci USA 1997; 44(7):3195–9.
13. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ and Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24(1):1–8.
14. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforminggrowth factor type beta1. Hum Mol Genet 1999; 8(1):93-7.
15. Hoffmann SC, Stanley EM, Darrin CE, Craighead N, DiMercurio BS, Koziol DE, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 2001; 72(8):1444–50.
16. Hosseini Farahabadi S, Tavakkol-Afshari J, Ganjali R,Rafatpanah H, Ghaffari J, Farid-Hosseini R. Association between the Polymorphism of TGF-β1 Gene Promoter (-509C>T) and Idiopathic Chronic Urticaria. Iran J Allergy Asthma Immunol 2006; 5(3):109-13.
17. Kinane DF, Shiba H, Hart TC. The genetic basis of periodontitis. Periodontol 2000 2005; 39:91-117
18. Brett PM, Zygogianni p, Griffiths GS, Tomaz M, Parkar M, Aiuto FD, et al. Functional Gene Polymorphisms in Aggressive and Chronic Periodontitis. J Dent Res 2005;84(12):1149-53.
19. Mellati E, Arab HR, Tavakkol-Afshari J, Ebadian AR, Radvar M. Analysis of – 1082 IL-10 gene polymorphism in Iranian patients with generalized aggressive periodontitis. Med Sci Monit 2007; 13(11):CR510-14.
20. Kiani Z, Tavakkol-Afshari J, Hojjat H, Arab HR, Radvar M, Sadeghizadeh M, et al. Polymorphism of IL-1α (-889) gene and its association with Aggressive periodontitis. Iran J Allergy Asthma Immunol 2009; 8(2):95-8.
21. Baradaran Rahimi H, Radvar M, Arab HR, Tavakkol Afshari J, Ebadian AR. Association of Interleukin-1Receptor Antagonist Gene Polymorphisms With Generalized Aggressive Periodontitis in an Iranian Population. J Periodontol 2010; 81(9):1342-6.
22. Dutra WO, Moreira PR, Souza PEA, Gollob KJ, Gomez RS. Implications of cytokine gene polymorphisms on the orchestration of the immune response: Lessons learned from oral diseases. Cytokine Growth Factor Rev 2009;20(3):223–32.
23. Fiebig A, Jepsen S, Loos BG, Scholz C, Schafer C, Ruhling A, et al. Polymorphisms in the interleukin-1 (IL1) gene cluster are not associated with aggressive periodontitis in a large Caucasian population. Genomics 2008; 92(5):309-15.
24. Sakellari D, Katsares V, Georgiadou M, Kouvatsi A, Arsenakis M,Konstantinidis A. No correlation of five gene polymorphisms with periodontal conditions in a Greek population. J Clin Periodontol 2006;33(11):765-70.
25. Gore EA, Sanders JJ, Pandey JP, Palesch Y, Galbraith GM. Interleukin-1beta+3953 allele 2: association with disease status in adult periodontitis. J Clin Periodontol 1998; 25(10):781–5.
26. Kaarthikeyan G, Jayakumar ND, Padmalatha O, Sheeja V, Sankari M, Anandan B. Analysis of the association between interleukin -1β (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. Indian J Dent Res 2009; 20(1):37-40.
27. Craandijk J, van Krugten MV, Verweij CL, van der Velden U, Loos BG .Tumor necrosis factor-alpha gene Gene Polymorphisms of TNF-α and IL-1β and Generalized Aggressive Periodontitis polymorphisms in relation to periodontitis. J Clin Periodontol 2002; 29(1):28–34.
28. Menezes NG, Colombo APV. Lack of association between the TNF-α -308 G/A genetic polymorphism and periodontal disease in Brazilians. Braz Oral Res 2008;22(4):322-7.
29. Guzeldemir E, Gunhun M, Ozcelik O, Tastan H.Interluekin 1 and tumor necrosis factor-α gene polymorphism in Turkish patients with localized aggressive periodontitis. J oral science 2008; 50 (2):151-9.
30. Soga Y, Nishimura F, Ohyama H, Maeda H, Takashiba S, Murayama Y. Tumor necrosis factor-alpha gene (TNF- alpha) -1031/-863, -857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese. J Clin Periodontol 2003; 30(6):524-31.
31. McGuire MK, Nunn ME. Prognosis versus actual outcome. IV the effectiveness of clinical parameters and IL-1 genotype in accurately predicting prognoses and tooth survival. J Periodontol 1999; 70(1):49-56.
32. Erciyas K, Pehlivan S, Sever T, Igci M, Arslan A, Orbak R. Association between TNF-alpha, TGF-beta1, IL-10, IL-6 and IFN-gamma gene polymorphisms and generalized aggressive periodontitis. Clin Invest Med 2010; 33(2):E85.
33. Rogers MA, Figliomeni L, Baluchova K, Tan AES, Davis G, Henry PJ, et al. Do Interleukin-1 polymorphisms predict the development of periodontitis or the success of dental implants? J periodontal Res 2002; 37(1):37-41.
34. Gonçalves LS, Ferreira SMS, Souza CO, Colombo APV. Influence of IL-1 gene polymorphism on the periodontal microbiota of HIV-infected Brazilian individuals. Braz Oral Res 2009; 23(4):452-9.
35. Saleh TA, Stephen L, Kotze M, Pretorius A. The composite interleukin-1 genotype in South Africa. SADJ 2009; 64(4):170-3.
36. Zhang D, Zheng H, Zhou Y, Tang X, Yu B, Li J.Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer 2007; 7:45.
37. Kumar S, Kumar A, Kumar Dixit V. Evidences showing association of interleukin-1B polymorphisms with increased risk of gastric cancer in an Indian population. Biochem Biophys Res Commun 2009; 387(3):456–60.
38. Hausen AZ, Crusius BA, Murillo LS, Alizadeh B, Morre AZ, Meijer CJLM et al. IL-1B promoter polymorphism and epstein-barr virus in Dutch patients with gastric carcinoma. Int J Cancer 2003; 107:866–7.
39. Cauci S, Di Santolo M, Ryckman KK, Williams SM, Banfi G. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status. BMC Med Genet 2010; 1:29.
40. Kumar R, Goswami R, Agarwal S, Israni N, Singh SK, Rani R. Association and interaction of the TNF-alpha gene with other pro- and anti-inflammatory cytokine genes and HLA genes in patients with type 1 diabetes from North India. Tissue Antigens 2007; 69(6):557–67.
41. Riha RL, Yang LA, Rabnott GC, Tunnicliffe AM, Fong KM, Zimmerman PV. Cytokine gene polymorphisms in idiopathic pulmonary fibrosis. Internal Med J 2004;34(3):126–9.
42. Fan HM, Wang Z, Feng FM, Zhang KL, Yuan JX, Sui H, et al. Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis. Biomed Environ Sci 2010; 23(2):137-45.
43. Montazeri S, Nalliah S, Radhakrishnan AK. Is there a genetic variation association in the IL-10 and TNF apromoter gene with gestational diabetes mellitus? Hereditas 2010; 147(2):94–102.
44. Trujillo-Murillo K, Pérez-Ibave D, Muñoz-Mejía C, Cordero-Pérez P, Muñoz-Espinosa L, Martínez- Rodríguez H, et al. Prevalence of the -308 and -238 tumor necrosis factor alpha (TNF-á) promoter polymorphisms in mexican chronic hepatitis C patients. Rev Gastroenterol Mex 2010; 75(1):7-11.
45. Ross OA, Curran MD, Rea IM, Hyland P, Duggan O, Barnett CR, et al. HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish. Mech Ageing Dev 2003; 124(4):563-7.

Files
IssueVol 12, No 4 (2013) QRcode
SectionArticles
Keywords
Aggressive periodontitis Gene polymorphism Interleukin-1 beta Tumor Necrosis Factor alpha

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Ebadian AR, Radvar M, Tavakkol Afshari J, Sargolzaee N, Brook A, Ganjali R, Tamizi M, Arab HR. Gene Polymorphisms of TNF-α and IL-1β Are Not Associated with Generalized Aggressive Periodontitis in an Iranian Subpopulation. Iran J Allergy Asthma Immunol. 1;12(4):345-351.