Molecular Biology Reports

, Volume 39, Issue 10, pp 9319–9329 | Cite as

Association of the IL-10 polymorphisms and periodontitis: a meta-analysis

  • C. M. AlbuquerqueEmail author
  • A. J. Cortinhas
  • F. J. Morinha
  • J. C. Leitão
  • C. A. Viegas
  • E. M. Bastos


No clear consensus has been reached regarding the association of IL-10 polymorphisms and periodontitis. Therefore, we performed a meta-analysis of case–control studies and a systemic review in an effort to systematically summarize the existing knowledge. Studies were identified by searching PubMed database until December 2011. IL-10 −1082 (−1087) A>G, −819 (−824) C>T and −592 (−597) C>A polymorphisms were included in the present meta-analysis. We calculated the specific odds ratios along with their 95 % confidence intervals to compare the distribution of alleles and genotypes between cases and controls. An additive “per-allele” model (major allele vs. minor allele) was performed, and dominant and recessive models were also considered. The random-effects model was applied for the analysis. Cumulative analysis was also performed. Heterogeneity and publication bias were assessed. Nine case–control studies involving 841 periodontitis cases (644 chronic periodontitis and 197 aggressive periodontitis cases) and 748 controls were included. We found statistically significant association of IL-10 −819 (−824) C>T and IL-10 −592 (−597) C>A polymorphisms in Caucasians. The IL-10 −819 (−824) T and −592 (−597) A alleles may confer a relative increase in the risk for chronic periodontitis in Caucasians. Future studies may be important to reinforce these findings.


Interleukin-10 Meta-analysis Periodontitis Polymorphism 



This work was partially supported by the PhD grant SFRH/BD/44490/2008 of the Science and Technology Foundation (FCT) from Portugal.


  1. 1.
    Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820PubMedCrossRefGoogle Scholar
  2. 2.
    Papapanou RN, Lindhe J (2003) Epidemiology of periodontal diseases. In: Lindhe J, Karring T, Lang NP (eds) Clinical periodontology and implant dentistry, 4th edn. Blackwell, Oxford, pp 50–80Google Scholar
  3. 3.
    Kinane DF, Hart TC (2003) Gene and gene polymorphisms associated with periodontal disease. Crit Rev Oral Biol Med 14:430–449PubMedCrossRefGoogle Scholar
  4. 4.
    Van Dyke TE, Dave S (2005) Risk factors for periodontitis. J Int Acad Periodontol 7:3–7PubMedGoogle Scholar
  5. 5.
    Michalowicz BS, Diehl SR, Gunsolley JC, Sparks BS, Brooks CN, Koertge TE, Califano JV, Burmeister JA, Schenkein HA (2000) Evidence of a substantial genetic basis for risk of adult periodontitis. J Periodontol 71:1699–1707PubMedCrossRefGoogle Scholar
  6. 6.
    American Academy of Periodontology (1999) The pathogenesis of periodontal diseases (position paper). J Periodontol 70:457–470CrossRefGoogle Scholar
  7. 7.
    Preshaw PM, Taylor JJ (2011) How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol 38(Suppl 11):60–84PubMedCrossRefGoogle Scholar
  8. 8.
    Kinane DF, Shiba H, Hart TC (2005) The genetic basis of periodontitis. Periodontol 2000 39:91–117PubMedCrossRefGoogle Scholar
  9. 9.
    Tatakis DN, Kumar PS (2005) Etiology and pathogenesis of periodontal disease. Dent Clin North Am 49:491–516PubMedCrossRefGoogle Scholar
  10. 10.
    Kinane DF, Preshaw PM, Loos BG (2011) Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions—consensus of the seventh European workshop of periodontology. J Clin Periodontol 38(Suppl 11):44–48PubMedCrossRefGoogle Scholar
  11. 11.
    Smith AJP, Humphries SE (2009) Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev 20:43–59PubMedCrossRefGoogle Scholar
  12. 12.
    Stabholz A, Soskolne WA, Shapira L (2010) Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol 2000 53:138–153PubMedCrossRefGoogle Scholar
  13. 13.
    Yoshie H, Kobayashi T, Tai H, Galicia JC (2007) The role of genetic polymorphisms in periodontitis. Periodontology 2000 43:102–132PubMedCrossRefGoogle Scholar
  14. 14.
    Brett PM, Zygogianni P, Griffiths GS, Tomaz M, Parkar M, D’Aiuto F, Tonetti M (2005) Functional gene polymorphisms in aggressive and chronic periodontitis. J Dent Res 84:1149–1153PubMedCrossRefGoogle Scholar
  15. 15.
    Babel N, Cherepnev G, Babel D, Tropmann A, Hammer M, Volk H-D, Reinke P (2006) Analysis of tumor necrosis factor-α, transforming growth factor-β, interleukin-10, IL-6, and interferon-γ gene polymorphisms in patients with chronic periodontitis. J Periodontol 77:1978–1983PubMedCrossRefGoogle Scholar
  16. 16.
    Berglundh T, Donati M, Mahn-Zorii M, Hanson L-A, Padyukov L (2003) Association of the −1087 IL 10 gene polymorphism with severe chronic periodontitis in Swedish Caucasians. J Clin Periodontol 30:249–254PubMedCrossRefGoogle Scholar
  17. 17.
    Sumer AP, Kara N, Keles GC, Gunes S, Koprulu H, Bagci H (2007) Association of interleukin-10 gene polymorphisms with severe generalized chronic periodontitis. J Periodontol 78:493–497PubMedCrossRefGoogle Scholar
  18. 18.
    Scarel-Caminaga RM, Trevilatto PC, Souza AP, Brito RB, Camargo LEA, Line SRP (2004) Interleukin-10 gene promoter polymorphisms are associated with chronic periodontitis. J Clin Periodontol 31:443–448PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang K, Hei P, Deng L, Lin J (2007) Interleukin-10 gene promoter polymorphisms and their protein production in peritoneal fluid in patients with endometriosis. Mol Hum Reprod 13:135–140PubMedCrossRefGoogle Scholar
  20. 20.
    Ma SL, Tang NL, Lam LC, Chiu HF (2005) The association between promoter polymorphism of the interleukin-10 gene and Alzheimer’s disease. Neurobiol Aging 26:1005–1010PubMedCrossRefGoogle Scholar
  21. 21.
    Gaudreault N, Ducharme V, Lamontagne M, Guauque-Olarte S, Mathieu P, Pibarot P, Bossé Y (2011) Replication of genetic association studies in aortic stenosis in adults. Am J Cardiol 108(9):1305–1310PubMedCrossRefGoogle Scholar
  22. 22.
    Fowler EV, Eri R, Hume G, Johnstone S, Pandeya N, Lincoln D, Templeton D, Radford-Smith GL (2005) TNF alpha and IL10 SNPs act together to predict disease behavior in Crohn’s disease. J Med Genet 42:523–528PubMedCrossRefGoogle Scholar
  23. 23.
    Liu N, Lu H, Tao F, Guo T, Liu C, Cui B, Ning G (2011) An association of interleukin-10 gene polymorphisms with Graves’ disease in two Chinese populations. Endocrine 40(1):90–94PubMedCrossRefGoogle Scholar
  24. 24.
    Stanilova SA, Miteva LD, Karakolev ZT, Stefanov CS (2006) Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility. Intensive Care Med 32:260–266PubMedCrossRefGoogle Scholar
  25. 25.
    Trikalinos TA, Salanti G, Zintzaras E, Ioannidis JP (2008) Meta-analysis methods. Adv Genet 60:311–334PubMedCrossRefGoogle Scholar
  26. 26.
    Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33(2):177–182PubMedCrossRefGoogle Scholar
  27. 27.
    Nikolopoulos GK, Dimou NL, Hamodrakas SJ, Bagos PG (2008) Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. J Clin Periodontol 35:754–767PubMedCrossRefGoogle Scholar
  28. 28.
    Ozturk A, Vieira AR (2009) TLR4 as a risk factor for periodontal disease: a reappraisal. J Clin Periodontol 36:279–286PubMedCrossRefGoogle Scholar
  29. 29.
    Shao M, Huang P, Cheng R, Hu T (2009) Interleukin-6 polymorphisms modify the risk of periodontitis: a systematic review and meta-analysis. J Zhejiang Univ Sci B 10(12):920–927PubMedCrossRefGoogle Scholar
  30. 30.
    Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9):1291–1306PubMedCrossRefGoogle Scholar
  31. 31.
    Cochran W (1954) The combination of estimates from different experiments. Biometrics 10(1):101–129CrossRefGoogle Scholar
  32. 32.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327(7414):557–560PubMedCrossRefGoogle Scholar
  33. 33.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRefGoogle Scholar
  34. 34.
    Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634PubMedCrossRefGoogle Scholar
  35. 35.
    Mellati E, Arab HR, Tavakkol-Afshari J, Ebadian AR, Radvar M (2007) Analysis of −1082 IL-10 gene polymorphism in Iranian patients with generalized aggressive periodontitis. Med Sci Monit 13(11):CR510–CR514PubMedGoogle Scholar
  36. 36.
    Claudino M, Trombone APF, Cardoso CR, Ferreira SB Jr, Martins W Jr, Assis GF, Santos CF, Trevilatto PC, Campanelli AP, Silva JS, Garlet GP (2008) The broad effects of the functional IL-10 promoter −592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome. J Leukoc Biol 84:1565–1573PubMedCrossRefGoogle Scholar
  37. 37.
    Reichert S, Machulla HKG, Klapproth J, Zimmermann U, Reichert Y, Gläser CH, Schaller HG, Stein J, Schulz S (2008) The interleukin-10 promoter haplotype ATA is a putative risk factor for aggressive periodontitis. J Periodontal Res 43:40–47PubMedGoogle Scholar
  38. 38.
    Hu K-F, Huang K-C, Ho Y-P, Lin Y-C, Ho K-Y, Wu Y-M, Yang Y-H, Tsai C-C (2009) Interleukin-10 (−592 C/A) and interleukin-12B (+16974 A/C) gene polymorphisms and the interleukin-10 ATA haplotype are associated with periodontitis in a Taiwanese population. J Periodontal Res 44:378–385PubMedCrossRefGoogle Scholar
  39. 39.
    Kinane DF, Hodge P, Eskdale J, Ellis R, Gallagher G (1999) Analysis of genetic polymorphisms at the interleukin-10 and tumour necrosis factor loci in early-onset periodontitis. J Periodontal Res 34(7):379–386PubMedCrossRefGoogle Scholar
  40. 40.
    Yamazaki K, Tabeta K, Nakajima T, Ohsawa Y, Ueki K, Itoh H, Yoshie H (2001) Interleukin-10 gene promoter polymorphism in Japanese patients with adult and early-onset periodontitis. J Clin Periodontol 28:828–832PubMedCrossRefGoogle Scholar
  41. 41.
    Gonzales JR, Michel J, Diete A, Herrmann JM, Bödeker RH, Meyle J (2002) Analysis of genetic polymorphisms at the interleukin-10 loci in aggressive and chronic periodontitis. J Clin Periodontol 29:816–822PubMedCrossRefGoogle Scholar
  42. 42.
    Loos BG, John RP, Laine ML (2005) Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol 32(Suppl. 6):159–179PubMedCrossRefGoogle Scholar
  43. 43.
    de Sá AR, Moreira PR, Xavier GM, Sampaio I, Kalapothakis E, Dutra WO, Gomez RS (2007) Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses. Int Endod J 40:563–572PubMedCrossRefGoogle Scholar
  44. 44.
    Savarrio L, Donati M, Carr C, Kinane DF, Berglundh T (2007) Interleukin-24, RANTES and CCR5 gene polymorphisms are not associated with chronic adult periodontitis. J Periodontal Res 42:152–158PubMedCrossRefGoogle Scholar
  45. 45.
    Cullinan MP, Westerman B, Hamlet SM, Palmer JE, Faddy MJ, Seymour GJ, Middleton PG, Taylor JJ (2008) Progression of periodontal disease and interleukin-10 gene polymorphism. J Periodontal Res 43:328–333PubMedCrossRefGoogle Scholar
  46. 46.
    Donati M, Liljenberg B, Padyukov L, Berglundh T (2008) Local expression of interleukin-10 and mCD14 in relation to the −1087 IL-10 and −159 CD14 gene polymorphisms in chronic periodontitis. J Periodontol 79:517–524PubMedCrossRefGoogle Scholar
  47. 47.
    Erciyas K, Pehlivan S, Sever T, Igci M, Arslan A, Orbak R (2010) Association between TNF-α, TGF-β1, IL-10, IL-6 and IFN-γ gene polymorphisms and generalized aggressive periodontitis. Clin Invest Med 33(2):E85–E91PubMedGoogle Scholar
  48. 48.
    Haverkamp MH, Lindeboom JA, de Visser AW, Kremer D, Kuijpers TW, van de Vosse E, van Dissel JT (2010) Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in The Netherlands: relevance of polymorphisms in candidate host immunity genes. Int J Pediatr Otorhinolaryngol 74(7):752–754PubMedCrossRefGoogle Scholar
  49. 49.
    Passoja A, Puijola I, Knuuttila M, Niemelä O, Karttunen R, Raunio T, Tervonen T (2010) Serum levels of interleukin-10 and tumour necrosis factor-α in chronic periodontitis. J Clin Periodontol 37(10):881–887PubMedCrossRefGoogle Scholar
  50. 50.
    Larsson L, Thorbert-Mros S, Rymo L, Berglungh T (2011) Interleukin-10 (Il-10) genotypes of the −1087 single nucleotide polymorphism influence Sp1 expression in periodontitis lesions. J Periodontol. doi: 10.1902/jop.2011.100623
  51. 51.
    Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4(1):1–6PubMedCrossRefGoogle Scholar
  52. 52.
    Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P (1999) 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 42:1101–1108PubMedCrossRefGoogle Scholar
  53. 53.
    Hirose M, Ishihara K, Saito A, Nakagawa T, Yamada S, Okuda K (2001) Expression of cytokines and inducible nitric oxide synthase in inflamed gingival tissue. J Periodontol 72(5):590–597PubMedCrossRefGoogle Scholar
  54. 54.
    Suárez LJ, Ocampo AM, Dueñas RE, Rodríguez A (2004) Relative proportions of T-cell subpopulations and cytokines that mediate and regulate the adaptative immune response in patients with aggressive periodontitis. J Periodontol 75(9):1209–1215PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • C. M. Albuquerque
    • 1
    • 2
    Email author
  • A. J. Cortinhas
    • 3
  • F. J. Morinha
    • 1
    • 4
  • J. C. Leitão
    • 3
  • C. A. Viegas
    • 2
    • 5
  • E. M. Bastos
    • 1
    • 6
  1. 1.Centre of Genetics and BiotechnologyUniversity of Trás-os-Montes and Alto Douro, Institute for Biotechnology and Bioengineering (CGB-UTAD/IBB)Vila RealPortugal
  2. 2.Department of Veterinary Sciences, Agricultural and Veterinary Sciences SchoolUniversity of Trás-os-Montes e Alto DouroVila RealPortugal
  3. 3.Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD)University of Trás-os-Montes and Alto DouroVila RealPortugal
  4. 4.Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB)University of Trás-os-Montes and Alto DouroVila RealPortugal
  5. 5.3B’s Research Group: Biomaterials, Biodegradables and Biomimetics, Department of Polymer EngineeringUniversity of MinhoTaipas, GuimarãesPortugal
  6. 6.Department of Genetics and Biotechnology, Life and Ambient Sciences SchoolUniversity of Trás-os-Montes e Alto DouroVila RealPortugal

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