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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

General Research Article

Analysis of Interleukin-1 Receptor Antagonist Variable Number Tandem Repeat Variant in Recurrent Aphthous Stomatitis

Author(s): Akin Tekcan, Serbulent Yigit*, Ayse F. Nursal, Mehmet K. Tumer, Kaan Yerliyurt and Nilufer Kuruca

Volume 21, Issue 1, 2021

Published on: 13 April, 2020

Page: [139 - 144] Pages: 6

DOI: 10.2174/1871530320666200413092239

Price: $65

Abstract

Background/Aims: Recurrent aphthous stomatitis (RAS) is one of the common oral inflammatory diseases. As immunological and genetic factors have been held responsible for the pathogenesis of RAS, the objective of this study was to determine whether the interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) variant is a risk factor for the development of RAS in Turkish patients and to define its contribution to the increased risk.

Methods: The IL-1Ra VNTR variant was evaluated in 169 RAS patients and 171 healthy controls by the polymerase chain reaction (PCR) method.

Results: No statistically significant difference was found in the genotype distributions and allele frequencies of IL-1Ra VNTR variant between RAS patients and healthy controls.

Conclusion: Lack of association between IL-1Ra VNTR variant and RAS could indicate that IL-1Ra has no significant role in the pathophysiology of RAS. However, it still appears to be very worthwhile to continue to search for cytokine gene variants in order to predict the development of such disease.

Keywords: Aphthous stomatitis, proinflammatory cytokines, Interleukin-1 Receptor Antagonist, polymerase chain reaction, variable number tandem repeat, variant.

Graphical Abstract
[1]
Field, E.A.; Allan, R.B. Review article: oral ulceration--aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic. Aliment. Pharmacol. Ther., 2003, 18(10), 949-962.
[http://dx.doi.org/10.1046/j.1365-2036.2003.01782.x] [PMID: 14616160]
[2]
Natah, S.S.; Konttinen, Y.T.; Enattah, N.S.; Ashammakhi, N.; Sharkey, K.A.; Häyrinen-Immonen, R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int. J. Oral Maxillofac. Surg., 2004, 33(3), 221-234.
[http://dx.doi.org/10.1006/ijom.2002.0446] [PMID: 15287304]
[3]
Stenman, G.; Heyden, G. Premonitory stages of recurrent aphthous stomatitis. I. Histological and enzyme histochemical investigations. J. Oral Pathol., 1980, 9(3), 155-162.
[http://dx.doi.org/10.1111/j.1600-0714.1980.tb00372.x] [PMID: 6776249]
[4]
Häyrinen-Immonen, R. Immune-activation in recurrent oral ulcers (ROU). Scand. J. Dent. Res., 1992, 100(4), 222-227.
[PMID: 1439527]
[5]
Bazrafshani, M.R.; Hajeer, A.H.; Ollier, W.E.; Thornhill, M.H. IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes Immun., 2002, 3(5), 302-305.
[http://dx.doi.org/10.1038/sj.gene.6363882] [PMID: 12140751]
[6]
Arend, W.P. Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J. Clin. Invest., 1991, 88(5), 1445-1451.
[http://dx.doi.org/10.1172/JCI115453] [PMID: 1834696]
[7]
Granowitz, E.V.; Clark, B.D.; Mancilla, J.; Dinarello, C.A. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J. Biol. Chem., 1991, 266(22), 14147-14150.
[PMID: 1830582]
[8]
Borra, R.C.; Andrade, P.M.; Silva, I.D.; Morgun, A.; Weckx, L.L.; Smirnova, A.S.; Franco, M. The Th1/Th2 immune-type response of the recurrent aphthous ulceration analyzed by cDNA microarray. J. Oral Pathol. Med., 2004, 33(3), 140-146.
[http://dx.doi.org/10.1111/j.0904-2512.2004.00089.x] [PMID: 15128055]
[9]
Lewkowicz, N.; Lewkowicz, P.; Banasik, M.; Kurnatowska, A.; Tchórzewski, H. Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. Immunol. Lett., 2005, 99(1), 57-62.
[http://dx.doi.org/10.1016/j.imlet.2005.01.002] [PMID: 15894112]
[10]
Hu, Z.; Shao, M.; Chen, Y.; Zhou, J.; Qian, J.; Xu, L.; Ma, H.; Wang, X.; Xu, Y.; Lu, D.; Shen, H. Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer. Cancer Lett., 2006, 236(2), 269-275.
[http://dx.doi.org/10.1016/j.canlet.2005.05.015] [PMID: 16019127]
[11]
Tarlow, J.K.; Blakemore, A.I.; Lennard, A.; Solari, R.; Hughes, H.N.; Steinkasserer, A.; Duff, G.W. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum. Genet., 1993, 91(4), 403-404.
[http://dx.doi.org/10.1007/BF00217368] [PMID: 8500797]
[12]
Vijgen, L.; Van Gysel, M.; Rector, A.; Thoelen, I.; Esters, N.; Ceelen, T.; Vangoidsenhoven, E.; Vermeire, S.; Rutgeerts, P.; Van Ranst, M. Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease. Genes Immun., 2002, 3(7), 400-406.
[http://dx.doi.org/10.1038/sj.gene.6363888] [PMID: 12424621]
[13]
Ship, J.A.; Chavez, E.M.; Doerr, P.A.; Henson, B.S.; Sarmadi, M. Recurrent aphthous stomatitis. Quintessence Int., 2000, 31(2), 95-112.
[PMID: 11203919]
[14]
Karasneh, J.; Bani-Hani, M.; Alkhateeb, A.; Hassan, A.; Alzoubi, F.; Thornhill, M. TLR2, TLR4 and CD86 gene polymorphisms in recurrent aphthous stomatitis. J. Oral Pathol. Med., 2015, 44(10), 857-863.
[http://dx.doi.org/10.1111/jop.12298] [PMID: 25482673]
[15]
Buño, I.J.; Huff, J.C.; Weston, W.L.; Cook, D.T.; Brice, S.L. Elevated levels of interferon gamma, tumor necrosis factor alpha, interleukins 2, 4, and 5, but not interleukin 10, are present in recurrent aphthous stomatitis. Arch. Dermatol., 1998, 134(7), 827-831.
[http://dx.doi.org/10.1001/archderm.134.7.827] [PMID: 9681346]
[16]
Lang, N.P.; Tonetti, M.S.; Suter, J.; Sorrell, J.; Duff, G.W.; Kornman, K.S. Effect of interleukin-1 gene polymorphisms on gingival inflammation assessed by bleeding on probing in a periodontal maintenance population. J. Periodontal Res., 2000, 35(2), 102-107.
[http://dx.doi.org/10.1034/j.1600-0765.2000.035002102.x] [PMID: 10863964]
[17]
Arend, W.P. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev., 2002, 13(4-5), 323-340.
[http://dx.doi.org/10.1016/S1359-6101(02)00020-5] [PMID: 12220547]
[18]
Mohammadoo-Khorasani, M; Salimi, S; Tabatabai, E; Sandoughi, M; Zakeri, Z. Association of interleukin-1 receptor antagonist gene 86bp VNTR polymorphism with systemic lupus erythematosus in south east of Iran. Zahedan J, 2014, 16(Res Med Sci 12), 51.4.
[19]
Witkin, S.S.; Gerber, S.; Ledger, W.J. Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin. Infect. Dis., 2002, 34(2), 204-209.
[http://dx.doi.org/10.1086/338261] [PMID: 11740709]
[20]
Santtila, S.; Savinainen, K.; Hurme, M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand. J. Immunol., 1998, 47(3), 195-198.
[http://dx.doi.org/10.1046/j.1365-3083.1998.00300.x] [PMID: 9519856]
[21]
Kamenarska, Z.; Dzhebir, G.; Hristova, M.; Savov, A.; Vinkov, A.; Kaneva, R.; Mitev, V.; Dourmishev, L. IL-1RN VNTR Polymorphism in adult dermatomyositis and systemic lupus erythematosus. Dermatol. Res. Pract., 2014.2014953597
[http://dx.doi.org/10.1155/2014/953597] [PMID: 25328514]
[22]
Perrier, S.; Coussediere, C.; Dubost, J.J.; Albuisson, E.; Sauvezie, B. IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjögren’s syndrome and rheumatoid arthritis. Clin. Immunol. Immunopathol., 1998, 87(3), 309-313.
[http://dx.doi.org/10.1006/clin.1998.4520] [PMID: 9646842]
[23]
Aggarwal, A.; Srivastava, R.; Singh, S.; Kumar Dubey, P. IL1 gene polymorphisms in enthesitis related arthritis category of juvenile idiopathic arthritis (ERA-JIA). Clin. Rheumatol., 2012, 31(4), 607-611.
[http://dx.doi.org/10.1007/s10067-011-1898-8] [PMID: 22124790]
[24]
Agrawal, S.; Srivastava, R.; Sharma, B.; Pandya, S.; Misra, R.; Aggarwal, A. IL1RN*2 allele of IL-1receptor antagonist VNTR polymorphism is associated with susceptibility to ankylosing spondylitis in Indian patients. Clin. Rheumatol., 2008, 27(5), 573-576.
[http://dx.doi.org/10.1007/s10067-007-0748-1] [PMID: 17899305]
[25]
Mittal, R.D.; Bid, H.K.; Ghoshal, U.C. IL-1 receptor antagonist (IL-1Ra) gene polymorphism in patients with inflammatory bowel disease in India. Scand. J. Gastroenterol., 2005, 40(7), 827-831.
[http://dx.doi.org/10.1080/00365520510015629] [PMID: 16109659]
[26]
Najafi, S.; Yousefi, H.; Mohammadzadeh, M.; Bidoki, A.Z.; Firouze Moqadam, I.; Farhadi, E.; Amirzargar, A.A.; Rezaei, N. Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis. Int. J. Immunogenet., 2015, 42(6), 428-431.
[http://dx.doi.org/10.1111/iji.12228] [PMID: 26385127]
[27]
Guimarães, A.L.; de Sá, A.R.; Victória, J.M.; Correia-Silva, J.F.; Pessoa, P.S.; Diniz, M.G.; Gomez, R.S. Association of interleukin-1β polymorphism with recurrent aphthous stomatitis in Brazilian individuals. Oral Dis., 2006, 12(6), 580-583.
[http://dx.doi.org/10.1111/j.1601-0825.2006.01243.x] [PMID: 17054771]
[28]
Kalkan, G.; Yigit, S.; Karakus, N.; Baş, Y.; Seçkin, H.Y. Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients. Gene, 2013, 527(1), 207-210.
[http://dx.doi.org/10.1016/j.gene.2013.05.053] [PMID: 23756192]
[29]
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(2), 173-180.
[http://dx.doi.org/10.1007/s00403-013-1406-x] [PMID: 23982631]
[30]
Wu, D.; Xin, J.; Liu, J.; Zhou, P. The association between interleukin polymorphism and recurrent aphthous stomatitis: A meta-analysis. Arch. Oral Biol., 2018, 93, 3-11.
[http://dx.doi.org/10.1016/j.archoralbio.2018.05.011] [PMID: 29800802]
[31]
Chen, L.; Ke, Z.; Zhou, Z.; Jiang, X.; Zhao, Y.; Zhang, J. Associations of IL-1, 6, and 10 gene polymorphisms with susceptibility to recurrent aphthous stomatitis: insights from a meta-analysis. Genet. Test. Mol. Biomarkers, 2018, 22(4), 237-245.
[http://dx.doi.org/10.1089/gtmb.2017.0072] [PMID: 29641282]
[32]
Bazrafshani, M.R.; Hajeer, A.H.; Ollier, W.E.; Thornhill, M.H. Polymorphisms in the IL-10 and IL-12 gene cluster and risk of developing recurrent aphthous stomatitis. Oral Dis., 2003, 9(6), 287-291.
[http://dx.doi.org/10.1034/j.1601-0825.2003.00965.x] [PMID: 14629328]
[33]
Ślebioda, Z.; Kowalska, A.; Rozmiarek, M.; Krawiecka, E.; Szponar, E.; Dorocka-Bobkowska, B. The absence of an association between Interleukin 1β gene polymorphisms and recurrent aphthous stomatitis (RAS). Arch. Oral Biol., 2017, 84, 45-49.
[http://dx.doi.org/10.1016/j.archoralbio.2017.09.013] [PMID: 28942153]
[34]
Yakar, T.; Serin, E.; Coşar, A.M.; Arslan Taş, D.; Ataç, F.B. The relationship of recurrent aphthous stomatitis and Helicobacter pylori, cytokine gene polymorphism and cobalamin. Turk. J. Gastroenterol., 2015, 26(4), 304-308.
[http://dx.doi.org/10.5152/tjg.2015.0161] [PMID: 26039006]

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