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Erschienen in: Archives of Dermatological Research 2/2014

01.03.2014 | Original Paper

Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis

verfasst von: Nevin Karakus, Serbulent Yigit, Aydin Rustemoglu, Goknur Kalkan, Nihan Bozkurt

Erschienen in: Archives of Dermatological Research | Ausgabe 2/2014

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Abstract

Recurrent aphthous stomatitis (RAS) is a common disease with oral ulceration in which cytokines are thought to play an important role. High levels of interleukin (IL)-6, a pro-inflammatory cytokine have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if the IL-6 gene polymorphisms are associated with RAS or clinical characteristics of RAS in a cohort of Turkish population. 184 RAS patients and 150 healthy controls were included in the study. The genotypes of IL-6 gene −572G>C and −174G>C polymorphisms were determined using polymerase chain reaction based restriction fragment length polymorphism analysis. The genotype frequencies of −572G>C polymorphism showed statistically significant differences between RAS patients and controls (p = 0.01). Frequencies of GG + GC genotypes and G allele of −572G>C polymorphism were found higher in RAS patients (p = 0.0001, OR 10.8, 95 % CI 2.79–70.5; p = 0.0008, OR 2.06, 95 % CI 1.35–3.17, respectively). The genotype frequencies of −174G>C polymorphism also showed statistically significant differences between RAS patients and controls (p < 0.0001). Frequencies of GG genotype and G allele of −174G>C polymorphism were found higher in RAS patients (p < 0.0001, OR 4.87, 95 % CI 3.06–7.85; p < 0.0001, OR 3.82, 95 % CI 2.64–5.59, respectively). GG–GG combined genotype and G–G haplotype of −174G>C to −572G>C loci were also significantly higher in RAS patients (p < 0.0001 and p = 1.5 × 10−8, respectively). After stratifying clinical and demographical characteristics of RAS patients according to IL-6 gene polymorphisms, an association was observed between family history of RAS and −174G>C polymorphism (p = 0.011). Susceptibility effects of both IL-6 gene −572G>C and −174G>C polymorphisms for RAS were observed. Further studies are necessary to prove the association of IL-6 gene polymorphisms with RAS.
Literatur
1.
Zurück zum Zitat Amano Y, Lee SW, Allison AC (1993) Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability. Mol Pharmacol 43:176–182PubMed Amano Y, Lee SW, Allison AC (1993) Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability. Mol Pharmacol 43:176–182PubMed
2.
Zurück zum Zitat Balding J, Healy CM, Livingstone WJ, White B, Mynett-Johnson L et al (2003) Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease? Genes Immun 4:533–540PubMedCrossRef Balding J, Healy CM, Livingstone WJ, White B, Mynett-Johnson L et al (2003) Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease? Genes Immun 4:533–540PubMedCrossRef
3.
Zurück zum Zitat Bazrafshani MR, Hajeer AH, Ollier WE, Thornhill MH (2002) IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes Immun 3(5):302–305PubMedCrossRef Bazrafshani MR, Hajeer AH, Ollier WE, Thornhill MH (2002) IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes Immun 3(5):302–305PubMedCrossRef
4.
Zurück zum Zitat Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E et al (2003) −174G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176PubMed Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E et al (2003) −174G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176PubMed
5.
Zurück zum Zitat Bowcock AM, Kidd JR, Lathrop GM, Daneshvar L, May LT et al (1988) The human “interferon-beta 2/hepatocyte stimulating factor/interleukin-6” gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8–16PubMedCrossRef Bowcock AM, Kidd JR, Lathrop GM, Daneshvar L, May LT et al (1988) The human “interferon-beta 2/hepatocyte stimulating factor/interleukin-6” gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics 3:8–16PubMedCrossRef
6.
Zurück zum Zitat Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L et al (2001) Interleukin-6 gene −174g > c and −572g > c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21:1458–1463PubMedCrossRef Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L et al (2001) Interleukin-6 gene −174g > c and −572g > c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21:1458–1463PubMedCrossRef
7.
Zurück zum Zitat Cussigh A, Falleti E, Fabris C, Bitetto D, Cmet S et al (2011) Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 63(1):33–41PubMedCrossRef Cussigh A, Falleti E, Fabris C, Bitetto D, Cmet S et al (2011) Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C. Immunogenetics 63(1):33–41PubMedCrossRef
8.
Zurück zum Zitat Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS et al (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCentralPubMedCrossRef Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS et al (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Gemmell E, Seymour GJ (2004) Immunoregulatory control of Th1/Th2 cytokine profiles in periodontal disease. Periodontol 2000 35:21–41PubMedCrossRef Gemmell E, Seymour GJ (2004) Immunoregulatory control of Th1/Th2 cytokine profiles in periodontal disease. Periodontol 2000 35:21–41PubMedCrossRef
10.
Zurück zum Zitat Guimarães AL, Correia-Silva Jde F, Sá AR, Victória JM, Diniz MG et al (2007) Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Biol 52(3):268–272PubMedCrossRef Guimarães AL, Correia-Silva Jde F, Sá AR, Victória JM, Diniz MG et al (2007) Investigation of functional gene polymorphisms IL-1beta, IL-6, IL-10 and TNF-alpha in individuals with recurrent aphthous stomatitis. Arch Oral Biol 52(3):268–272PubMedCrossRef
11.
Zurück zum Zitat Hirano T (1998) Interleukin 6 and its receptor: ten years later. Int Rev Immunol 16:249–284PubMedCrossRef Hirano T (1998) Interleukin 6 and its receptor: ten years later. Int Rev Immunol 16:249–284PubMedCrossRef
12.
Zurück zum Zitat Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford) 40:656–661CrossRef Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford) 40:656–661CrossRef
13.
Zurück zum Zitat Miller MF, Garfunkel AA, Ram C, Ship II (1977) Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol 43:886–891PubMedCrossRef Miller MF, Garfunkel AA, Ram C, Ship II (1977) Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol 43:886–891PubMedCrossRef
14.
Zurück zum Zitat Morse HR, Olomolaiye OO, Wood NA, Keen LJ, Bidwell JL (1999) Induced heteroduplex genotyping of TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine 11:789–795PubMedCrossRef Morse HR, Olomolaiye OO, Wood NA, Keen LJ, Bidwell JL (1999) Induced heteroduplex genotyping of TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine 11:789–795PubMedCrossRef
15.
Zurück zum Zitat Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA et al (2004) Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 33:221–234PubMedCrossRef Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA et al (2004) Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 33:221–234PubMedCrossRef
16.
Zurück zum Zitat Pekiner FN, Aytugar E, Demirel GY, Borahan MO (2012) Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of patients with Behçet’s disease and recurrent aphthous ulcerations. J Oral Pathol Med 41(1):73–79PubMedCrossRef Pekiner FN, Aytugar E, Demirel GY, Borahan MO (2012) Interleukin-2, interleukin-6 and T regulatory cells in peripheral blood of patients with Behçet’s disease and recurrent aphthous ulcerations. J Oral Pathol Med 41(1):73–79PubMedCrossRef
17.
Zurück zum Zitat Porter SR, Scully C, Pedersen A (1998) Recurrent aphthous stomatitis. Crit Rev Oral Biol Med 9:306–321PubMedCrossRef Porter SR, Scully C, Pedersen A (1998) Recurrent aphthous stomatitis. Crit Rev Oral Biol Med 9:306–321PubMedCrossRef
18.
Zurück zum Zitat Roitt IM, Lehner T (1983) Immunology of oral diseases, 2nd edn. Blackwell Scientific, Oxford Roitt IM, Lehner T (1983) Immunology of oral diseases, 2nd edn. Blackwell Scientific, Oxford
19.
Zurück zum Zitat Rowland TL, McHugh SM, Deighton J, Dearman RJ, Ewan PW et al (1998) Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology 40:11–20PubMedCrossRef Rowland TL, McHugh SM, Deighton J, Dearman RJ, Ewan PW et al (1998) Differential regulation by thalidomide and dexamethasone of cytokine expression in human peripheral blood mononuclear cells. Immunopharmacology 40:11–20PubMedCrossRef
20.
Zurück zum Zitat Scully C, Porter S (2008) Oral mucosal disease: recurrent aphthous stomatitis. Br J Oral Maxillofac Surg 46:198–206PubMedCrossRef Scully C, Porter S (2008) Oral mucosal disease: recurrent aphthous stomatitis. Br J Oral Maxillofac Surg 46:198–206PubMedCrossRef
21.
Zurück zum Zitat Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M (2000) Recurrent aphthous stomatitis. Quintessence Int 31:95–112PubMed Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M (2000) Recurrent aphthous stomatitis. Quintessence Int 31:95–112PubMed
22.
Zurück zum Zitat Song GG, Choi SJ, Ji JD, Lee YH (2013) Association between tumor necrosis factor-α promoter −308 A/G, −238 A/G, interleukin-6 −174 G/C and −572G/C polymorphisms and periodontal disease: a meta-analysis. Mol Biol Rep May 9 [Epub ahead of print] Song GG, Choi SJ, Ji JD, Lee YH (2013) Association between tumor necrosis factor-α promoter −308 A/G, −238 A/G, interleukin-6 −174 G/C and −572G/C polymorphisms and periodontal disease: a meta-analysis. Mol Biol Rep May 9 [Epub ahead of print]
23.
Zurück zum Zitat Stenman G, Heyden G (1980) Premonitory stages of recurrent aphthous stomatitis. I. Histological and enzyme histochemical investigations. J Oral Pathol 9:155–162PubMedCrossRef Stenman G, Heyden G (1980) Premonitory stages of recurrent aphthous stomatitis. I. Histological and enzyme histochemical investigations. J Oral Pathol 9:155–162PubMedCrossRef
24.
Zurück zum Zitat Taga T, Kishimoto T (1997) Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819PubMedCrossRef Taga T, Kishimoto T (1997) Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15:797–819PubMedCrossRef
25.
Zurück zum Zitat Tan D, Wu X, Hou M, Lee SO, Lou W et al (2005) Interleukin-6 polymorphism is associated with more aggressive prostate cancer. J Urol 174:753–756PubMedCrossRef Tan D, Wu X, Hou M, Lee SO, Lou W et al (2005) Interleukin-6 polymorphism is associated with more aggressive prostate cancer. J Urol 174:753–756PubMedCrossRef
26.
Zurück zum Zitat Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144PubMedCrossRef Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144PubMedCrossRef
27.
Zurück zum Zitat Tseng LH, Chen PJ, Lin MT, Singleton K, Martin EG et al (2002) Simultaneous genotyping of single nucleotide polymorphisms in the IL-6, IL-10, TNFalpha and TNFbeta genes. Tissue Antigens 59:280–286PubMedCrossRef Tseng LH, Chen PJ, Lin MT, Singleton K, Martin EG et al (2002) Simultaneous genotyping of single nucleotide polymorphisms in the IL-6, IL-10, TNFalpha and TNFbeta genes. Tissue Antigens 59:280–286PubMedCrossRef
28.
Zurück zum Zitat Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S et al (2006) Genetic risk for ischemic and hemorrhagic stroke. Arterioscler Thromb Vasc Biol 26:1920–1925PubMedCrossRef Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S et al (2006) Genetic risk for ischemic and hemorrhagic stroke. Arterioscler Thromb Vasc Biol 26:1920–1925PubMedCrossRef
29.
Zurück zum Zitat Yamamoto T, Yoneda K, Ueta E, Osaki T (1994) Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. Oral Surg Oral Med Oral Pathol 78:727–735PubMedCrossRef Yamamoto T, Yoneda K, Ueta E, Osaki T (1994) Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. Oral Surg Oral Med Oral Pathol 78:727–735PubMedCrossRef
30.
Zurück zum Zitat Zadik Y, Levin L, Shmuly T, Sandler V, Tarrasch R (2012) Recurrent aphthous stomatitis: stress, trait anger and anxiety of patients. J Calif Dent Assoc 40(11):879–883PubMed Zadik Y, Levin L, Shmuly T, Sandler V, Tarrasch R (2012) Recurrent aphthous stomatitis: stress, trait anger and anxiety of patients. J Calif Dent Assoc 40(11):879–883PubMed
Metadaten
Titel
Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis
verfasst von
Nevin Karakus
Serbulent Yigit
Aydin Rustemoglu
Goknur Kalkan
Nihan Bozkurt
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Dermatological Research / Ausgabe 2/2014
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-013-1406-x

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