Abstract
Genetic factors that predispose individuals to Behcet’s disease (BD) are considered to play an important role in the development of the disease. The serum level of tumor necrosis factor (TNF) is elevated in patients with BD, and a dramatic response to anti-TNF-α antibody treatment further supports the role of TNF in BD. We investigated the distribution of TNF-α promoter −1031T/C and −308G/A polymorphisms in 53 BD patients of Iranian Azeri Turks and 79 matched healthy controls, via the PCR–RFLP technique. The frequency of the TNF-α −1031C allele was significantly higher in Behcet’s patients than in healthy controls (p < 0.0001, OR = 3.08; 95% CI = 1.73–5.47), whereas the frequency of the TNF-α −308A allele was similar in the two compared groups. The frequency of CG haplotype was significantly higher (p < 0.0001, OR = 3.42; 95% CI = 1.89–6.18), and that of the TA haplotype was significantly lower in BD patients than in healthy controls. These results suggest that TNF-α is a susceptibility gene for BD in patients from Iranian Azeri Turk ethnic group.
Abbreviations
- BD:
-
Behcet’s disease
- TNF-α:
-
Tumor necrosis factor-alpha
- HLA:
-
Human leukocyte antigen
- PCR–RFLP:
-
Polymerase chain reaction–restriction fragment length polymorphism
References
Wallace GR, Kondeatis E, Vaughan RW, Verity DH, Chen Y, Fortune F et al (2007) IL-10 genotype analysis in patients with Behcet’s disease. Hum Immunol 68:122–127
Harmouche H, Maamar M, Sahnoune I, Tazi-Mezalek Z, Aouni M, Maaouni A (2007) Fever revealing Behcet’s disease: two new cases. Eur J Intern Med 18:146–147
Schwartz T, Langevitz P, Zemer D, Gazit E, Pras M, Livneh A (2000) Behcet’s disease in familial Mediterranean fever: characterization of the association between the two diseases. Semin Arthritis Rheum 29:286–295
Touitou I, Kone-Paut I (2008) Autoinflammatory diseases. Best Pract Res Clin Rheumatol 22:811–829
Gul A, Inanc M, Ocal L, Aral O, Konice M (2000) Familial aggregation of Behcet’s disease in Turkey. Ann Rheum Dis 59:622–625
Verity DH, Marr JE, Ohno S, Wallace GR, Stanford MR (1999) Behcet’s disease, the silk road and HLA-B51: historical and geographical perspectives. Tissue Antigens 54:213–220
Durrani K, Papaliodis GN (2008) The genetics of Adamantiades–Behcet’s disease. Semin Ophthalmol 23:73–79
Oztas MO, Onder M, Gurer MA, Bukan N, Sancak B (2005) Serum interleukin 18 and tumor necrosis factor-alpha levels are increased in Behcet’s disease. Clin Exp Dermatol 30:61–63
Ates A, Kinikli G, Duzgun N, Duman M (2006) Lack of association of tumor necrosis factor-alpha gene polymorphisms with disease susceptibility and severity in Behcet’s disease. Rheumatol Int 26:348–353
Higuchi T, Seki N, Kamizono S, Yamada A, Kimura A, Kato H et al (1998) Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens 51:605–612
Wilson AG, Symons JA, Mcdowell TL, Mcdevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation. Immunology 94:3195–3199
van Heel DA, Udalova IA, De Silva AP, Mc Govern DP, Kinouchi Y, Hull J et al (2002) Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-κB transcription factors. Hum Mol Genet 11:1281–1289
Christen U, Wolfe T, Mohrle U, Hughes AC, Rodrigo E, Green EA et al (2001) A dual role for TNF-α in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. J Immunol 166:7023–7032
Zuniga J, Vargas-Alarcon G, Hernandez-Pacheco G, Portal-Celhay C, Yamamoto-Furusho JK, Granados J (2001) Tumor necrosis factor-α promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). Genes Immun 2:363–366
International Study Group for Behcet’s Disease (1990) Criteria for diagnosis of Behcet’s disease. Lancet 335:1078–1080
Miller SA, Dynes DD, Polesky F (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Ahmad T, Wallace GR, James T, Neville M, Bunce M, Mulcahy-Hawes K et al (2003) Mapping the HLA association in Behcet’s disease: a role for tumor necrosis factor polymorphisms? Arthritis Rheum 48:807–813
Mizuki N, Ohno S, Sato T, Ishihara M, Miyata S, Nakamura S, Naruse T, Mizuki H, Tsuji K, Inoko H (1995) Microsatellite polymorphism located between the TNF and HLA-B genes in Behcet’s disease. Hum Immunol 43:129–135
Park K, Kim N, Nam J, Bang D, Lee ES (2006) Association of TNFA promoter region haplotype in Behcet’s disease. J Korean Med Sci 21:596–601
Lee EB, Kim JY, Lee YJ, Park MH, Song YW (2003) TNF and TNF receptor polymorphisms in Korean Behcet’s disease patients. Hum Immunol 64:614–620
Akman A, Sallakci N, Coskun M, Bacanli A, Yavuzer U, Alpsoy E et al (2006) TNF-a gene 1031 T/C polymorphism in Turkish patients with Behcet’s disease. Br J Dermatol 155:350–356
Kamoun M, Chelbi H, Houman MH, Lacheb J, Hamzaoui K (2007) Tumor necrosis factor gene polymorphisms in Tunisian patients with Behcet’s disease. Hum Immunol 68:201–205
Ben Dhifallah I, Houman H, Khanfir M, Hamzaoui K (2008) Endothelial nitric oxide synthase gene polymorphism is associated with Behcet’s disease in Tunisian population. Hum Immunol 69:661–665
Lee YJ, Kang SW, Song JK, Baek HJ, Choi HJ, Bae YD et al (2007) Associations between interferon regulatory factor-1 polymorphisms and Behcet’s disease. Hum Immunol 68:770–778
Sahin N, Bicakcigil M, Atagunduz P, Direskeneli H, Saruhan-Direskeneli G (2007) PTPN22 gene polymorphism in Behcet’s disease. Tissue Antigens 70:432–434
Baranathan V, Stanford MR, Vaughan RW, Kondeatis E, Graham E, Fortune F et al (2007) The association of the PTPN22 620 W polymorphism with Behcet’s disease. Ann Rheum Dis 66:1531–1533
Touitou I, Magne X, Molinari N, Navarro A, Le Quellec A, Picco P et al (2000) MEFV mutations in Behcet’s disease. Hum Mutat 16:271–272
Kone-Paut I, Sanchez E, Le Quellec A, Manna R, Touitou I (2007) Autoinflammatory gene mutations in Behcet’s disease. Ann Rheum Dis 66:832–834
Gul A (2005) Behcet’s disease as an autoinflammatory disorder. Curr Drug Targets Inflamm Allergy 4:81–83
Schlesselman J (1982) Case–control studies: design, conduct, analysis, equation 6.6 and 6.7: sample size determination with an unequal case–control ratio. Oxford, New York
Acknowledgments
The authors would like to thank all participating patients. This project was financially supported by Center of Excellence for Biodiversity (University of Tabriz).
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Bonyadi, M., Jahanafrooz, Z., Esmaeili, M. et al. TNF-α gene polymorphisms in Iranian Azeri Turkish patients with Behcet’s Disease. Rheumatol Int 30, 285–289 (2009). https://doi.org/10.1007/s00296-009-1134-x
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DOI: https://doi.org/10.1007/s00296-009-1134-x