Background. Periodontal disease leading to clinical findings such as increased periodontal probing depth involves a complex interaction between invading pathogenic microorganisms and the patient's immune system. Lymphotoxin alpha (LT-α) is a potent multifunctional immune modulator that contributes toward susceptibility to immune regulation disorders, including periodontal disease. Objective. In this study, we tested the hypothesis that chronic periodontitis (CP) is associated with polymorphisms of the LT-α gene. Materials and Methods. A total of 126 subjects, 44 healthy subjects, and 82 subjects with CP, were evaluated for periodontal disease by measuring clinical attachment loss and separation. Samples of epithelial cells were obtained for DNA analysis by scraping of the buccal mucosa. The LT-α gene was analyzed by polymerase chain reaction followed by endonuclease digestion with NcoI to analyze restriction fragment length polymorphisms. Results. The LT-α gene (+252A/G) polymorphism was associated with CP. LT-α allele frequencies were significantly different ( ) between patients with CP and healthy individuals, with an odds ratio of 2.67 for patients with CP with the G allele. Conclusions. These findings suggest the LT-α gene genotype is a risk indicator for susceptibility to chronic periodontal disease in the Brazilian population studied. 1. Introduction Periodontal disease is characterized by inflammatory destruction of tissues that support the tooth, leading to loss of epithelial attachment and destruction of the periodontal ligament, cementum, and alveolar bone, and eventually tooth loss [1]. Etiological studies show that although bacterial infection causes periodontitis, a subset of individuals show severe disease in the absence of a large bacterial load, suggesting that these individuals mount an exaggerated response to a modest microbial challenge. Thus, the patient’s immune response may play a critical role in periodontal disease pathogenesis and expression [1, 2]. This observation has led to interest in finding potential genetic markers of disease susceptibility, including polymorphisms in genes encoding key molecules of the host defense system, such as cytokines [3–5]. Lymphotoxin- (LT- ), previously known as tumor necrosis factor (TNF)- , is a proinflammatory cytokine encoded by the LT-α gene (HUGO Gene Nomenclature Committee, http://www.genenames.org/). LT- plays a key role in orchestrating the inflammatory and immune responses involved in tissue destruction and bone resorption and has been suggested to be an important participant in the
References
[1]
K. S. Kornman and H. L？e, “The role of local factors in the etiology of periodontal diseases,” Periodontology 2000, vol. 2, pp. 83–97, 1993.
[2]
R. A. Reinhardt, M. P. Masada, W. B. Kaldahl et al., “Gingival fluid IL-1 and IL-6 levels in refractory periodontitis,” Journal of Clinical Periodontology, vol. 20, no. 3, pp. 225–231, 1993.
[3]
Y. Shimada, H. Tai, M. Endo et al., “Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis,” Journal of Clinical Periodontology, vol. 31, no. 6, pp. 463–469, 2004.
[4]
R. M. Scarel-Caminaga, P. C. Trevilatto, A. P. Souza, R. B. Brito, and S. R. P. Line, “Investigation of IL4 gene polymorphism in individuals with different levels of chronic periodontitis in a Brazilian population,” Journal of Clinical Periodontology, vol. 30, no. 4, pp. 341–345, 2003.
[5]
K. Shibani, R. Shhab, and R. Khattab, “Analysis of IL-1α(-889) and IL-1B(+3953) gene polymorphism in Syrian patients with aggressive periodontitis: a pilot study,” ISRN Dentistry, vol. 2011, Article ID 682564, 5 pages, 2011.
[6]
R. C. Page, S. Offenbacher, H. E. Schroeder, G. J. Seymour, and K. S. Kornman, “Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions,” Periodontology 2000, vol. 1997, no. 14, pp. 216–248, 1997.
[7]
G. C. Armitage, “Development of a classification system for periodontal diseases and conditions.,” Annals of periodontology / the American Academy of Periodontology, vol. 4, no. 1, pp. 1–6, 1999.
[8]
G. Messer, U. Spengler, M. C. Jung et al., “Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-β gene correlates with a variant amino acid in position 26 and a reduced level of TNF-β production,” Journal of Experimental Medicine, vol. 173, no. 1, pp. 209–219, 1991.
[9]
V. Boraska, N. W. Rayner, C. J. Groves et al., “Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes,” BMC Medical Genetics, vol. 11, no. 1, p. 69, 2010.
[10]
J. L. Newton, S. M. J. Harney, A. E. Timms et al., “Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis,” Arthritis and Rheumatism, vol. 50, no. 7, pp. 2122–2129, 2004.
[11]
R. V. Albuquerque, C. M. Hayden, L. J. Palmer et al., “Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma,” Clinical and Experimental Allergy, vol. 28, no. 5, pp. 578–584, 1998.
[12]
K. Ozaki, Y. Ohnishi, A. Iida et al., “Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction,” Nature Genetics, vol. 32, no. 4, pp. 650–654, 2002.
[13]
R. Ramasawmy, K. C. Fae, E. Cunha-Neto et al., “Polymorphisms in the gene for lymphotoxin-α predispose to chronic chagas cardiomyopathy,” Journal of Infectious Diseases, vol. 196, no. 12, pp. 1836–1843, 2007.
[14]
A. Fassmann, L. I. Holla, D. Buckova, A. Vasku, V. Znojil, and J. Vanek, “Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population,” Journal of Periodontal Research, vol. 38, no. 4, pp. 394–399, 2003.
[15]
R. Ramasawmy, K. C. Fae, E. Cunha-Neto et al., “Polymorphisms in the gene for lymphotoxin-α predispose to chronic chagas cardiomyopathy,” Journal of Infectious Diseases, vol. 196, no. 12, pp. 1836–1843, 2007.
[16]
K. E. McColl, H. Watabe, and M. H. Derakhshan, “Sporadic gastric cancer; a complex interaction of genetic and environmental risk factors,” American Journal of Gastroenterology, vol. 102, no. 9, pp. 1893–1895, 2007.
[17]
P. C. Trevilatto and S. R. P. Line, “Use of buccal epithelial cells for PCR amplification of large DNA fragments,” Journal of Forensic Odonto-Stomatology, vol. 18, no. 1, pp. 6–9, 2000.
[18]
F. Stüber, M. Petersen, F. Bokelmann, and U. Schade, “A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-α concentrations and outcome of patients with severe sepsis,” Critical Care Medicine, vol. 24, no. 3, pp. 381–384, 1996.
[19]
G. P. Garlet, “Critical reviews in oral biology & medicine: destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints,” Journal of Dental Research, vol. 89, no. 12, pp. 1349–1363, 2010.
[20]
K. S. Kornman, R. C. Page, and M. S. Tonetti, “The host response to the microbial challenge in periodontitis: assembling the players,” Periodontology 2000, vol. 1997, no. 14, pp. 33–53, 1997.
[21]
T. C. Hart and K. S. Kornman, “Genetic factors in the pathogenesis of periodontitis,” Periodontology 2000, vol. 1997, no. 14, pp. 202–215, 1997.
[22]
P. C. Trevilatto, A. P. De Souza Pardo, R. M. Scarel-Caminaga et al., “Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians,” Archives of Oral Biology, vol. 56, no. 1, pp. 54–62, 2011.
[23]
S. Zhang, A. Crivello, S. Offenbacher, A. Moretti, D. W. Paquette, and S. P. Barros, “Interferon-gamma promoter hypomethylation and increased expression in chronic periodontitis,” Journal of Clinical Periodontology, vol. 37, no. 11, pp. 953–961, 2010.
[24]
R. M. Scarel-Caminaga, P. C. Trevilatto, A. P. Souza, R. B. Brito, and S. R. P. Line, “Investigation of IL4 gene polymorphism in individuals with different levels of chronic periodontitis in a Brazilian population,” Journal of Clinical Periodontology, vol. 30, no. 4, pp. 341–345, 2003.
[25]
A. P. de Souza, P. C. Trevilatto, R. M. Scarel-Caminaga, R. B. de Brito, S. P. Barros, and S. R. P. Line, “Analysis of the MMP-9 (C-1562 T) and TIMP-2 (G-418C) gene promoter polymorphisms in patients with chronic periodontitis,” Journal of Clinical Periodontology, vol. 32, no. 2, pp. 207–211, 2005.
[26]
R. B. de Brito Jr, R. M. Scarel-Caminaga, P. C. Trevilatto, A. P. de Souza, and S. Pereira Barros, “Polymorphisms in the vitamin D receptor gene are associated with periodontal disease,” Journal of Periodontology, vol. 75, no. 8, pp. 1090–1095, 2004.
[27]
M. J. Santos, D. Carmona-Fernandes, J. Caetano-Lopes et al., “TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus,” Rheumatology International, vol. 32, no. 8, pp. 2239–2244, 2012.
[28]
N. Karakus, N. Kara, A. N. Ulusoy, C. ？zaslan, and Y. Bek, “Tumor necrosis factor alpha and beta and interferon gamma gene polymorphisms in turkish breast cancer patients,” DNA and Cell Biology, vol. 30, no. 6, pp. 371–377, 2011.
