Review Article

Association between interleukin family gene polymorphisms and recurrent aphthous stomatitis risk

Published online:


The present study was aimed at identifying the association between interleukin family gene polymorphisms and recurrent aphthous stomatitis (RAS) risk using a meta-analysis. We searched the PubMed, web of science, Embase and ScienceDirect-Elsevier databases for research on the interleukin polymorphism and RAS risk. In total 12 studies were included to investigate the relationships between RAS risk and six polymorphisms by calculating pooled odds ratios (ORs) and 95% confidence intervals (CIs). A significant association was found between IL-1β+3954C/T polymorphism and RAS risk. A high risk of RAS was found in RAS patients with the G allele or GG genotype of IL-6−174 polymorphism. Low risk of RAS was found in the C allele of IL-10−592C/A polymorphism under an allele model, but a high risk of RAS was found in IL-10−1082G/A polymorphism. In the subgroup analysis, no correlation was found between the IL-10−1082 polymorphism and RAS risk in the caucasian population with the allele model. In conclusion, an IL-1β+3954C/T polymorphism was determined to be related to susceptibility to RAS, and individuals with the G allele and GG genotype of IL-6−174 or the A allele of IL-10−592 or the G allele of IL-10−1082 appeared to be more vulnerable to developing RAS.

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  1. 1.

    Ni Riordain R, McCreary C. Validity and reliability of a newly developed quality of life questionnaire for patients with chronic oral mucosal diseases. J Oral Pathol Med. 2011;40:604–9.

  2. 2.

    Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Hayrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg. 2004;33:221–34.

  3. 3.

    Zhang Jing WT, Ming Qi. Expression of transforming growth factor-β1 and interleukin-10 in patients with recurrent aphthous ulcer. J Pract Stomatol. 2014;30:82–4.

  4. 4.

    Zhang JING SJ, Gong Juan. Relationship between transforming growth factor-β1 and interleukin-10 single nucleotide polymorphism and susceptibility of recurrent aphthous ulcer. West China J Stomatol. 2016;34:27–31.

  5. 5.

    Bazrafshani MR, Hajeer AH, Ollier WE, Thornhill MH. IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes Immun. 2002;3:302–5.

  6. 6.

    Najafi S, Yousefi H, Mohammadzadeh M, Bidoki AZ, Firouze Moqadam I, Farhadi E, et al. Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis. Int J Immunogenet. 2015;42:428–31.

  7. 7.

    Sun M, Fu SM, Dong GY, Wu D, Wang GX, Wu Y. Inflammatory factors gene polymorphism in recurrent oral ulceration. J Oral Pathol Med. 2013;42:528–34.

  8. 8.

    Guimaraes AL, Correia-Silva Jde F, Sa AR, Victoria JM, Diniz MG, Costa Fde O, et al. Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Biol. 2007;52:268–72.

  9. 9.

    DSG. Meta-analysis: unsolved issues and future development. BMJ. 1998;316:221–5.

  10. 10.

    Jing C, Zhang JQ. Association between interleukin gene polymorphisms and risk of recurrent oral ulceration. Genet Mol Res. 2015;14:6838–43.

  11. 11.

    Bazrafshani MR, Hajeer AH, Ollier WE, Thornhill MH. Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis. Oral Dis. 2003;9:287–91.

  12. 12.

    Guimaraes AL, de Sa AR, Victoria JM, Correia-Silva JF, Pessoa PS, Diniz MG, et al. Association of interleukin-1beta polymorphism with recurrent aphthous stomatitis in Brazilian individuals. Oral Dis. 2006;12:580–3.

  13. 13.

    Najafi S, Firooze Moqadam I, Mohammadzadeh M, Bidoki AZ, Yousefi H, Farhadi E, et al. Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis. Immunol Invest. 2014;43:405–9.

  14. 14.

    Akman A, Ekinci NC, Kacaroglu H, Yavuzer U, Alpsoy E, Yegin O. Relationship between periodontal findings and specific polymorphisms of interleukin-1alpha and -1beta in Turkish patients with Behcet’s disease. Arch Dermatol Res. 2008;300:19–26.

  15. 15.

    Karakus N, Yigit S, Rustemoglu A, Kalkan G, Bozkurt N. Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis. Arch Dermatol Res. 2014;306:173–80.

  16. 16.

    Yakar T, Serin E, Cosar AM, Arslan Tas D, Atac FB. The relationship of recurrent aphthous stomatitis and Helicobacter pylori, cytokine gene polymorphism and cobalamin. Turk J Gastroenterol. 2015;26:304–8.

  17. 17.

    Contassot E, Beer HD, French LE. Interleukin-1, inflammasomes, autoinflammation and the skin. Swiss Med Wkly. 2012;142:w13590.

  18. 18.

    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.

  19. 19.

    Shirodaria S, Smith J, McKay IJ, Kennett CN, Hughes FJ. Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1alpha protein in gingival crevicular fluid of teeth with severe periodontal disease. J Dent Res. 2000;79:1864–9.

  20. 20.

    Nemetz A, Nosti-Escanilla MP, Molnar T, Kope A, Kovacs A, Feher J, et al. IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease. Immunogenetics. 1999;49:527–31.

  21. 21.

    Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nat Immunol. 2004;5:971–4.

  22. 22.

    McLoughlin RM, Witowski J, Robson RL, Wilkinson TS, Hurst SM, Williams AS, et al. Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation. J Clin Invest. 2003;112:598–607.

  23. 23.

    Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjogren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology. 2001;40:656–61.

  24. 24.

    Balding J, Healy CM, Livingstone WJ, White B, Mynett-Johnson L, Cafferkey M, et al. Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease? Genes Immun. 2003;4:533–40.

  25. 25.

    Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E, Scalerta R, et al. -174 G > C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res. 2003;9:2173–6.

  26. 26.

    Song GG, Choi SJ, Ji JD, Lee YH. Association between tumor necrosis factor-alpha 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;40:5191–203.

  27. 27.

    Kubin M, Kamoun M, Trinchieri G. Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. J Exp Med. 1994;180:211–22.

  28. 28.

    Eskdale J, Kube D, Gallagher G. A second polymorphic dinucleotide repeat in the 5’ flanking region of the human IL10 gene. Immunogenetics. 1996;45:82–3.

  29. 29.

    Eskdale J, Gallagher G. A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogenetics. 1995;42:444–5.

  30. 30.

    Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24:1–8.

  31. 31.

    Guo J, Jin M, Zhang M, Chen K. A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS ONE. 2012;7:e30585.

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Author information


  1. Department of Clinical Laboratory, General Hospital of Yangtze River Shipping, Wuhan, 430010, Hubei Province, China

    • Jun Wu
  2. Department of Clinical Laboratory, Longquanyi District of Chengdu Maternity and Child Health Care Hospital, Chengdu, 610100, Sichuan Province, China

    • Wei Wang


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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Wei Wang.