A familial case of Aggressive Periodontitis: clinical, microbiological and genetic findings
Caso familiar de Periodontite Agressiva: achados clínicos, microbiológicos e genéticos
Scarel-Caminaga, R.M.; Pires, J.R.; Sogumo, P.M.; Salmon, C.R.; Peres, R.C.R.; Spolidorio, D.M.P.
Rev. odontol. UNESP, vol.38, n3, p.175-183, 2009
Abstract
This study reports the clinical, microbiological and genetic findings in members of a Brazilian family with Aggressive Periodontitis (AgP). After periodontal exams in eleven members of the family, microbiological samples were collected from subgingival plaque and DNA were obtained from epithelial buccal cells. Polymerase Chain Reaction (PCR) was utilized to detect five species of periodontopathogens. PCR-RFLP (Restriction Fragment Length Polymorphism) and sequencing were used to investigate human polymorphisms in interleukin genes (IL4, IL10). Six members of the family showed Generalized AgP, four had Localized AgP and only one was considered unaffected by AgP. Aggregatibacter actinomycetemcomitans was the most prevalent pathogen (72.7%). The presence of Porphyromonas gingivalis was correlated with clinical findings (visible plaque, bleeding on probing and probing depth, p = 0.03). The genetic analyses revealed that 60% of the kindred affected by AgP showed specific IL4/ IL10 haplotypes combinations. The predominance of AgP in this family could be influenced by the amount of plaque and subgingival Aggregatibacter actinomycetemcomitans. Indeed, infection by Porphyromonas gingivalis was associated with clinical parameters of periodontitis. Although the majority of AgP family members presented at least one TTD/ ATA (IL4/ IL10) haplotype combination, it was unable to demonstrate an association with AgP.
Keywords
Periodontitis, microbiology, genetics, cytokines.
Resumo
Este estudo relata achados clínicos, microbiológicos e genéticos em indivíduos de uma família brasileira com Periodontite Agressiva (PA). Após exames periodontais realizados em onze membros da família, foram coletadas amostras microbiológicas de placa subgengival e DNA de células da mucosa oral. A Reação em Cadeia da Polimerase (do inglês, PCR) foi utilizada para detectar cinco espécies de periodontopatógenos. As técnicas do Polimorfismo por Comprimento de Fragmento de Restrição (RFLP) e sequenciamento foram usados para investigar polimorfismos humanos em genes da interleucina (IL4, IL10). Seis membros da família apresentaram PA Generalizada, quatro PA Localizada e apenas um indivíduo foi considerado não afetado pela PA. Aggregatibacter actinomycetemcomitans foi o patógeno prevalente (72,7%). A presença de Porphyromonas gingivalis foi relacionada com achados clínicos (placa visível, sangramento à sondagem e profundidade de sondagem, p = 0,03). A análise genética revelou que 60% dos membros da família afetados pela PA carregavam o mesmo haplótipo formado por uma combinação de alelos dos genes IL4/ IL10. O predomínio de PA nesta família pode ter sido influenciada pela quantidade de placa bacteriana e prevalência de Aggregatibacter actinomycetemcomitans presente no sulco gengival. A infecção por Porphyromonas gingivalis pode ser associada com parâmetros clínicos relacionados a periodontite. Embora a maioria dos membros afetados pela PA tenha apresentado pelo menos uma combinação de haplótipos TTD/ ATA (IL4/ IL10), não foi possível demonstrar estatisticamente uma associação com PA.
Palavras-chave
Periodontite, microbiologia, genética, citocinas.
References
1. Tonetti MS, Mombelli A. Early-onset periodontitis. Ann Periodontol. 1999;4:39-52.
2. Llorente MA, Griffiths GS. Periodontal status among relatives of aggressive periodontitis patients and reliability of family history report. J Clin Periodontol. 2006;33:121-5.
3. Page RC, Vandersteen GE, Ebersole JL, Williams BL, Dixon IL, Altman LC. Clinical and laboratory studies of a family with high prevalence of juvenile periodontitis. J Periodontol. 1985;66:602-10.
4. Marazita ML, Burmeister LC, Gunsolley JC, Koertge TE, Lake K, Schenkein HA. Evidence for autosomal dominant inheritance and race-specific heterogeneity in earlyonset periodontitis. J Periodontol. 1994;65:623-30.
5. Beaty TH, Boughman JA, Yang P, Astemborski JA, Suzuki JB. Genetic analysis of juvenile periodontitis in families ascertained through an affected proband. Am J Hum Genet. 1987;40:443-52.
6. Hodge PJ, Teaque PW, Wright AF, Kiane DF. Clinical and genetic analysis of a large north European Caucasian family affected by early-onset periodontitis. J Dent Res. 2000;79:857-63.
7. Loos BG, John RP, Laine ML. Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol. 2005;32:159-79.
8. Tai H, Endo M, Shimada Y, Gou E, Kobayashi T, Yamazaki K, et al. Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese. J Clin Periodontol. 2002;29:882-8.
9. Michel J, Gonzáles JR, Wunderlich D, Herrmann JM, Meyle J. Interlekin-4 polymorphisms in early-onset periodontitis. J Clin Periodontol. 2001;28:483-8.
10. Kinane DF, Hart TC. Genes and gene polymorphisms associated with periodontal disease. Crit Rev Oral Biol Med. 2003;14:430-49.
11. Kamma JJ, Nakou M, Gmür R, Baehni PC. Microbiological profile of early onset/ aggressive periodontitis patients. Oral Microbiol Immunol. 2004;19:314-21.
12. Timmerman MF, van der Weijden GA, Arief EM, Armand S, Abbas F, Winkel EG, et al. Untreated periodontal disease in Indonesian adolescents. Subgingival microbiota in relation to experienced progression of periodontits. J Clin Periodontol. 2001;28:617-27.
13. Mullaly BH, Dace B, Schelburne CE, Wolff LF, Coulter WA. Prevalence of periodontal pathogens in localized and generalized forms of early onset periodontitis. J Periodontal Res. 2000;35:232-41.
14. Papapanou PN, Baelum V, Luan WM, Madianos PN, Chen X, Fejerskov O, et al. Subgingival microbiota in adult Chinese: prevalence and relation to periodontal disease progression. J Periodontol. 1997;68:651-66.
15. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent Jr RL. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25:134-44.
16. Lang NP, Bartold PM, Cullinam M, Jeffcoat M, Mombelli A, Murakami S, et al.. Consensus Report: aggressive periodontitis. Ann Periodontol. 1999;4:53.
17. Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol. 1967;38:610-6.
18. Savitt ED, Strzempko MN, Vaccaro KK, Peros WJ, French CK. Comparison of cultural methods and DNA probe analyses for the detection of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in subgingival plaque samples. J Periodontol. 1988;59:431-8.
19. Benkirane RR, Guillot E, Mouton C. Immunonagnetic PCR and DNA probe for detection and identification of Porphyromonas gingivalis. J Clin Microbiol. 1995;33:2908-12.
20. Ashimoto A, Chen, C, Bakker I, Slots J. Polymerase chain reaction 8 putative periodontal pathogens in subgingival plaque of gingivitis and advanced periodontitis lesions. Oral Microbiol Immunol. 1996;11:266-73.
21. Guillot E, Mouton C. PCR-DNA probe assays for identification and detection of Prevotella intermedia sensu strictu and Prevotella nigrescens. J Clin Microbiol. 1997;35:1876-82.
22. Ávila-Campos MJ, Velásquez-Meléndez G. Prevalence of putative periodontopathogens from periodontal patients and healthy subjects in São Paulo, SP, Brasil. Rev Inst Med Trop Sao Paulo. 2002;44:1-5.
23. Rosalem Jr W, de Souza RC, de Andrade AFB, Colombo APV. Analysis of leukotoxin gene types of Actinobacillus actinomycetemcomitans in Brazilians with aggressive periodontitis. Braz J Microbiol. 2006;7:127-34.
24. Sambrook J, Russel DW. Molecular cloning: a laboratory manual. 3rd ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2001.
25. Scarel-Caminaga RM, Trevilatto PC, Souza AP, Brito Jr RB, Camargo LEA, Line SRP. Interleukin 10 gene promoter polymorphisms are associated with chronic periodontitis. J Clin Periodontol. 2004;31:443-8.
26. Scarel-Caminaga RM, Trevilatto PC, Souza AP, Brito Jr RB, Line SRP. Investigation of IL4 gene polymorphism in individuals with different levels of chronic periodontitis in a Brazilian population. J Clin Periodontol. 2003;30:587-91.
27. Noguchi E, Nukaga-Nishio Y, Jian Z, Yokuchi Y, Kamioka M, Yamakawa-Kobayashi K, et al. Haplotypes of the 5’ region of the IL-4 gene SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma. Hum Immunol. 2001;62:1251-7.
28. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnot PJ, Hutchinson I. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24:1-8.
29. Sanguinetti CJ, Neto ED, Simpson AJG. Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. BioTechniques. 1994;17:915-9.
30. Peres MA, Antunes JLF, Boing AF, Peres KG, Bastos JLD. Skin colour is associated with periodontal disease in Brazilian adults: a population-based oral health survey. J Clin Periodontol. 2007;34:196-201.
31. Levin L, Baev V, Lev R, Stabholz A, Ashkenazi M. Aggressive periodontitis among young Israeli army personnel. J Periodontol. 2006;77:1392-6.
32. Cortelli JR, Cortelli SC, Jordan SF, Haraszthy VI, Zambon JJ. Prevalence of periodontal pathogens in Brazilians with aggressive or chronic periodontitis. J Clin Periodontol. 2005;32:860-6.
33. Tinoco EMB, Beldi MI, Loureiro CA, Lana M, Campedelli F, Tinoco NM, et al. Localized juvenile periodontitis and Actinobacillus actinomycetemcomitans in a Brazilian population. Eur J Oral Sci. 1997;105:9-14.
34. Zambon JJ, Christersson LA, Slots J. Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patient groups and distribution of biotypes and serotypes within families. J Periodontol. 1983;54:707-11.
35. Slots J, Ting M. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 2000. 1999;20:82-121.
36. Socranky SS, Haffajee AD. The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol. 1992;63:322-31.
37. Schacher B, Baron F, Roβberg M, Wohlfeil M, Arndt R, Eickholz P. Aggregatibacter actinomycetemcomitanns as indicator for aggressive periodontitis by two analysing strategies. J Clin Periodontol. 2007;34:566-73.
38. Dogan B, Kipalev AS, Okte E, Sultan N, Asikainen SE. Consistent intrafamilial transmission of Actinobacillus actinomycetemcomitans despite clonal diversity. J Periodontol. 2008;79:307-15.
39. Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 1994;5:78-111.
40. Haffajee AD, Cugini MA, Dibart S, Smith C, Kent Jr RL, Socransky SS. Clinical and microbiological features of subjects with adult periodontitis who responded poorly to scaling and root planning. J Clin Periodontol. 1997;24:767-76.
41. Darby IB, Hodge PJ, Riggio MP, Kinane DF. Microbial comparison of smoker and non-smoker adult and early-onset periodontitis patients by polymerase chain reaction. J Clin Periodontol. 2000;27:417-24.
42. Trevilatto PC, Tramontina VA, Machado MAN, Gonçalves RB, Sallum AW, Line SRP. Clinical, genetic and microbiological findings in a Brazilian family with aggressive periodontitis. J Clin Periodontol. 2002;29:233-9.
43. Kornman KS, Crane A, Wang HY, Di Giovine FS, Newman MG, Pirk FW, et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol. 1997;24:72-7.
44. Shapira L, Wilensky A, Kinane DF. Effect of genetic variability on the inflammatory response to periodontal infection. J Clin Periodontol. 2005;32:72-86.
45. Yamazaki K, Tabeta K, Nakajima T, Ohsawa Y, Ueki K, Itoh H, et al. Interleukin-10 gene promoter polymorphism in Japanese patients with adult and early-onset periodontitis. J Clin Periodontol. 2001;28:828-32.
46. Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P. Polymorphic haplotypes of the interleukin- 10 5’ flanking region determine variable interleukin- 10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum. 1999;42:1101-8.
47. Gonzales JR, Michel J, Diete A, Herrmann JM, Böedeker RH, Meyle J. Analysis of genetic polymorphisms at the interleukin-10 loci in aggressive and chronic periodontitis. J Clin Periodontol. 2002;29:816-22.
48. Shapira L, van Dyke TE, Hart TC. A localized absence of interleukin-4 triggers Periodontal disease activity: a novel hypothesis. Med Hypoth. 1992;39:319-22.
49. Alaeddine N, DiBattista JA, Pelletier JP, Kiansa K, Clouter JM, Martel-Pelletier J. Inhibition of TNF- induced PGE2 production by anti-inflammatory cytokines IL-4, IL-10 and IL-13 in osteoarthritic synovial fibroblasts: distinct targeting in signaling pathways. Arthritis Rheum. 1999;42:710-20.
50. Bozkurt FY, Ay ZY, Berker E, Tepe E, Akkus S. Antiinflammatory cytokines in gingival crevicular fluid in patients with periodontitis and rheumatoid arthritis: a preliminary report. Cytokine. 2006;35:180-5.
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email