Original Article
 

HLA-DRB and HLA-DQB Allele and Haplotype Frequencies in Iranian Patients with Recurrent Aphthous Stomatitis

Abstract

Recurrent aphthous stomatitis (RAS) is known as the most common chronic disease of the oral cavity, which affects a range of 5-25% of the population. RAS appears to be associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. This study attempts to survey the distribution of HLA-DRB and -DQB alleles among Iranian RAS patients and healthy controls. In order to evaluate the association of HLA-DR and DQ alleles and haplotypes, 54 patients with RAS and 100 unrelated healthy subjects as control group were investigated. Our data indicated that DRB1*13:17, DRB1*15:01, and DRB5*01 were significantly more frequent in RAS patients in comparison to controls. However, DRB3:01allele frequency was higher in the controls compared to the patients. The significantly frequent allele in the patients compared with the healthy subjects was HLA-DQB1*03:02. However, both HLA-DQB1*02:01 and HLA-DQB1*03:01 alleles were most frequent in the healthy individuals rather than the patients. The DRB*04/DQB1*03:01 and DRB*01:01/DQB1*02:01 haplotypes were significantly distributed in healthy subjects compared with patients. However, DRB*07:01/DQB1*03:02 haplotype was found to be significantly frequent in patients than controls. In respect of HLA genes, factors are involved in the incidence of RAS; various HLA-DRB and HLA-DQB1 alleles and the related haplotypes are suggested to be the three main RAS susceptibility factors in our population study.

1. Tunes RS, Anjos TC, Martins GB, Barreto ER, Santiago MB. Prevalence of Behcet’s syndrome in patients with recurrent aphthous ulcerations in Brazil. Rheumatol Int 2009; 29(8):875-8.

2. Alpsoy E, Donmez L, Onder M, Gunasti S, Usta A, Karincaoglu Y, et al. Clinical features and natural course of Behçet’s disease in 661 cases: a multicentre study. Br J Dermatol 2007; 157(5):901-6.

3. Jurge S, Kuffer R, Scully C, Porter SR. Number VI recurrent aphthous stomatitis. Oral Dis 2006; 12(1):1-21.

4. Dolby A. Recurrent aphthous ulceration: Effect of sera and peripheral blood lymphocytes upon oral epithelial tissue culture cells. Immunology 1969; 17(5):709-14.

5. Lehner T. Immunoglobulin estimation of blood and saliva in human recurrent oral ulceration. Arch Oral Biol 1969;14(4):351-64.

6. Burnett PR, Wray D. Lytic effects of serum and mononuclear leukocytes on oral epithelial cells in recurrent aphthous stomatitis. Clin Immunol Immunopathol 1985; 34(2):197-204.

7. Graykowski EA, Barile MF, Lee WB, Stanley HR Jr.Recurrent aphthous stomatitis: clinical, therapeutic, histopathologic, and hypersensitivity aspects. Jama 1966;196(7):637-44.

8. Hasan A, Shinnick T, Mizushima Y, van der Zee R,Lehner T. Defining a T‐cell epitope within HSP 65 in recurrent aphthous stomatitis. Clin Exp Immunol 2002;128(2):318-25.

9. Sun A, Chia JS, Chiang CP. Chiang, Increased proliferative response of peripheral blood mononuclear cells and T cells to Streptococcus mutans and glucosyltransferase D antigens in the exacerbation stage of recurrent aphthous ulcerations. J Formos Med Assoc 2002; 101(8):560-6.

10. Lehner T. Autoimmunity in oral diseases, with special reference to recurrent oral ulceration. Proc R Soc Med 1968; 61(5):515-24.

11. Davidson A, Diamond B. Autoimmune diseases. N Engl J Med 2001; 345(5):340-50.

12. Albanidou-Farmaki E, Deligiannidis A, Markopoulos AK, Katsares V, Farmakis K, Parapanissiou E. HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance? Int J Immunogenet 2008; 35(6):427-32.

13. Challacombe SJ, Batchelor JR, Kennedy LA, Lehner T.HLA antigens in recurrent oral ulceration. Arch Dermatol 1977; 113(12):1717-19.

14. Lehner T. Immunologic aspects of recurrent oral ulcers.Oral Surgery, Oral Medicine, Oral Surg Oral Med Oral Pathol 1972; 33(1):80-5.

15. Lehner T, Welsh KI, Batchelor JR. The relationship of HLA-B and DR phenotypes to Behcet's syndrome, recurrent oral ulceration and the class of immune complexes. Immunology 1982; 47(4):581-7.

16. Miller, S., D. Dykes, and H. Polesky, A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3):1215.

17. Amirzargar AA, Khosravi F, Dianat SS, Alimoghadam K,

Ghavamzadeh F, Ansaripour B, et al. Association of HLA class II allele and haplotype frequencies with chronic myelogenous leukemia and age-at-onset of the disease. Pathol Oncol Res 2007; 13(1):47-51.
18. Olerup O, Zetterquist H. HLA‐DR typing by PCR amplification with sequence‐specific primers (PCR‐SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor‐recipient matching in cadaveric transplantation. Tissue antigens 1992; 39(5):225-35.
19. Amirzargar A, Mytilineos J, Farjadian S, Doroudchi M, Scherer S, Opelz G, et al. Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Hum Immunol 2001; 62(11):1234-8.
20. Ship II. Inheritance of aphthous ulcers of the mouth. J Dent Res 1965; 44(5):837-44.
21. Miller MF, Garfunkel AA, Ram C, Ship II. Inheritance patterns in recurrent aphthous ulcers: twin and pedigree data. Oral Surg Oral Med Oral Pathol 1977; 43(6):886-91.
22. Rogers RS. Recurrent aphthous stomatitis: clinical characteristics and evidence for an immunopathogenesis. J Invest Dermatol 1977; 69(6):499-509.
23. Scully C, Porter S. Oral mucosal disease: recurrent aphthous stomatitis. Br J Oral Maxillofac Surg 2008; 46(3):198-206.
24. Akman A, Sallakci N, Coskun M, Bacanli A, Yavuzer U, Alpsoy E, et al. TNF‐α gene 1031 T/C polymorphism in Turkish patients with Behçet's disease. Br J Dermatol 2006; 155(2):350-6.
25. 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(5):302-5.
26. 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(6):287-91.
27. Guimarães AL, Correia-Silva Jde F, Sá AR, Victória JM, Diniz MG, Costa Fde O, et al. Investigation of functional gene polymorphisms IL-1β, IL-6, IL-10 and TNF-α in individuals with recurrent aphthous stomatitis. Arch Oral Biol 2007; 52(3):268-72.
28. Alkhateeb A, Karasneh J, Abbadi H, Hassan A, Thornhill M. Association of cell adhesion molecule gene polymorphisms with recurrent aphthous stomatitis. J Oral Pathol Med 2013; 42(10):741-6.
29. Karasneh JA, Baszrafshani R, Thornhill M, Ollier WE. Endothelial nitric oxide synthase gene polymorphisms are

not associated with recurrent aphthous stomatitis. Arch Oral Biol 2009; 54(6):583-7.
30. Oksel F, Keser G, Ozmen M, Aksu K, Kitapcioglu G, Berdeli A, et al. Endothelial nitric oxide synthase gene Glu298Asp polymorphism is associated with Behcet's disease. Clin Exp Rheumatol 2005; 24(5 Suppl 42):S79-82.
31. Victoria JM1, Correia-Silva Jde F, Pimenta FJ, Kalapothakis E, Gomez RS. Serotonin transporter gene polymorphism (5‐HTTLPR) in patients with recurrent aphthous stomatitis. J Oral Pathol Med 2005; 34(8):494-7.
32. Borra RC, Andrade PM, Silva ID, Morgun A, Weckx LL, Smirnova AS, et al. The Th1/Th2 immune‐type response of the recurrent aphthous ulceration analyzed by cDNA microarray. J Oral Pathol Med 2004; 33(3):140-6.
33. Lewkowicz N, Lewkowicz P, Banasik M, Kurnatowska A, Tchórzewski H. Predominance of production of Th1 type cytokines in recurrent aphthous ulceration. Immunol Lett 2005; 99(1):57-62.
34. Lewkowicz N, Kur B, Kurnatowska A, Tchorzewski H, Lewkowicz P. Expression of Th1/Th2/Th3/Th17-related genes in recurrent aphthous ulcers. Arch Immunol Ther Exp (Warsz) 2011; 59(5):399-406.
35. Wilhelmsen NS, Weber R, Monteiro F, Kalil J, Miziara ID. Correlation between histocompatibility antigens and recurrent aphthous stomatitis in the Brazilian population. Braz J Otorhinolaryngol 2009; 75(3):426-31.
36. Özdemir, M., et al., HLA-B* 51 in patients with recurrent aphthous stomatitis. Acta Derm Venereol 2009; 89(2):202-3.
37. Ozdemir M, Acar H, Deniz F, Tümer E, Engin B, Balasar O. HLA-B* 51 in patients with recurrent aphthous stomatitis. Acta dermato-venereologica 2009; 89(2):202-3.
38. Gallina G, Cumbo V, Messina P, Caruso C. HLA-A, B, C, Dr, MT, and MB antigens in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1985; 59(4):364-70.
39. Platz P, Ryder LP, Donatsky O. Donatsky, No deviations of HLA-A and-B antigens in patients with recurrent aphthous stomatitis. Tissue antigens 1976; 8(4):279-80.

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IssueVol 15, No 4 (2016) QRcode
SectionOriginal Article(s)
Keywords
Allele frequency Haplotype frequency Human leukocyte antigen Recurrent aphthous stomatitis

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How to Cite
1.
Najafi S, Mohammadzadeh M, Zare Bidoki A, Meighani G, Aslani S, Mahmoudi M, Rezaei N. HLA-DRB and HLA-DQB Allele and Haplotype Frequencies in Iranian Patients with Recurrent Aphthous Stomatitis. Iran J Allergy Asthma Immunol. 2016;15(4):289-295.