Genetics of Behçet’s Disease

  • Ahmet Gül
  • Shigeaki Ohno


Behçet’s disease (BD) is a multifactorial disease with a strong genetic background. Varying frequencies of patients with a positive family history for BD were described with a tendency for higher figures in the Middle Eastern, juvenile-onset and HLA-B51 positive patients. Sibling recurrence risk ratio (λs) was calculated to be 11.4–52.5 for BD patients in Turkey. BD is strongly associated with a class I major histocompatibility complex (MHC) allele, HLA-B51, and this association was confirmed in various ethnic groups. Distribution of HLA-B51 allele in healthy population is suggested to play a role in the disease clustering in an area extending from the Mediterranean basin to Japan. The pathogenic mechanisms of HLA-B51 are still unknown, but it may include presentation of specific peptides to CD8+ cells and interaction with KIR3DL1 receptors. Although contribution of the HLA-B locus to the overall BD susceptibility was estimated to be 19%, other MHC associations including HLA-A26 and MICA*009 may have additive effects. Association studies also suggested several non-HLA disease susceptibility genes. However, only a few of them, including polymorphisms in the TNF, MEFV, ICAM1, and eNOS genes, were replicated in different ethnic groups. A linkage study in multicase families of Turkish origin revealed several possible susceptibility loci for BD with >3.0 nonparametric linkage scores at chromosome 12p12-13, 6p22-24, and 6q25-26. Recent genomewide association study using microsatellite markers in Japanese patients and controls confirmed the loci at 12p12 and 6q25, and it also suggested two additional loci at 3p12 and 22q11.22. Currently, results of genomewide association studies from different ethnic groups are being awaited to clarify the genetics of BD further.


Behçet’s disease Familial aggregation Sibling recurrence risk ratio (λs) HLA-B51 MICA HLA-A26 Linkage study Genomewide association study 


  1. 1.
    Gül A (2001) Behçet’s disease: an update on the pathogenesis. Clin Exp Rheumatol 19(Suppl 24):S6–S12PubMedGoogle Scholar
  2. 2.
    Zierhut M, Mizuki N, Ohno S et al (2003) Immunology and functional genomics of Behçet’s disease. Cell Mol Life Sci 60:1903–1922PubMedCrossRefGoogle Scholar
  3. 3.
    Fowler TJ, Humpston DJ, Nussey AM, Small M (1968) Behçet’s syndrome with neurological manifestations in two sisters. Br Med J 2:473–474PubMedCrossRefGoogle Scholar
  4. 4.
    Mason RM, Barnes CG (1969) Behçet’s syndrome with arthritis. Ann Rheum Dis 28:95–103PubMedCrossRefGoogle Scholar
  5. 5.
    Fadli ME, Youssef MM (1973) Neuro-Behçet’s syndrome in the United Arab Republic. Eur Neurol 9:76–89PubMedCrossRefGoogle Scholar
  6. 6.
    Chajek T, Fainaru M (1975) Behçet’s disease: report of 41 cases and a review of the literature. Medicine (Baltimore) 54:179–196CrossRefGoogle Scholar
  7. 7.
    Goolamali SK, Comaish JS, Hassanyeh F (1976) Familial Behçet’s syndrome. Br J Dermatol 95:637–642PubMedCrossRefGoogle Scholar
  8. 8.
    Nahir M, Scharf Y, Gidoni O et al (1978) HL-A antigens in Behçet’s disease. A family study. Dermatologica 156:205–208PubMedCrossRefGoogle Scholar
  9. 9.
    Abdel-Aziz AH, Fairburn EA (1978) Familial Behçet’s syndrome. Cutis 21:649–652PubMedGoogle Scholar
  10. 10.
    Dündar SV, Gencalp U, Simsek H (1985) Familial cases of Behçet’s disease. Br J Dermatol 113:319–321PubMedCrossRefGoogle Scholar
  11. 11.
    Chajek-Shaul T, Pisanty S, Knobler H et al (1987) HLA-B51 may serve as an immunogenetic marker for a subgroup of patients with Behçet’s syndrome. Am J Med 83:666–672PubMedCrossRefGoogle Scholar
  12. 12.
    Akpolat T, Koc Y, Yeniay I et al (1992) Familial Behçet’s disease. Eur J Med 1:391–395PubMedGoogle Scholar
  13. 13.
    Villanueva JL, Gonzalez-Dominguez J, Gonzalez-Fernandez R et al (1993) HLA antigen familial study in complete Behçet’s syndrome affecting three sisters. Ann Rheum Dis 52:155–157PubMedCrossRefGoogle Scholar
  14. 14.
    Nishiura K, Kotake S, Ichiishi A, Matsuda H (1996) Familial occurrence of Behçet’s disease. Jpn J Ophthalmol 40:255–259PubMedGoogle Scholar
  15. 15.
    Nishiyama M, Nakae K, Umehara T (2001) A study of familial occurrence of Behçet’s disease with and without ocular lesions. Jpn J Ophthalmol 45:313–316PubMedCrossRefGoogle Scholar
  16. 16.
    Fietta P (2005) Behçet’s disease: familial clustering and immunogenetics. Clin Exp Rheumatol 23(Suppl 38):S96–S105PubMedGoogle Scholar
  17. 17.
    Gül A, Inanc M, Ocal L et al (2000) Familial aggregation of Behçet’s disease in Turkey. Ann Rheum Dis 59:622–625PubMedCrossRefGoogle Scholar
  18. 18.
    Treudler R, Orfanos CE, Zouboulis CC (1999) Twenty-eight cases of juvenile-onset Adamantiades-Behçet’s disease in Germany. Dermatology 199:15–19PubMedCrossRefGoogle Scholar
  19. 19.
    Koné-Paut I, Geisler I, Wechsler B et al (1999) Familial aggregation in Behçet’s disease: high frequency in siblings and parents of pediatric probands. J Pediatr 135:89–93PubMedCrossRefGoogle Scholar
  20. 20.
    Hayasaka S, Kurome H, Noda S (1994) HLA antigens in a Japanese family with Behçet’s disease. Graefes Arch Clin Exp Ophthalmol 232:589–590PubMedCrossRefGoogle Scholar
  21. 21.
    Nishiyama M, Nakae K, Kuriyama T et al (2002) A study among related pairs of Japanese patients with familial Behçet’s disease: group comparisons by interval of disease onsets. J Rheumatol 29:743–747PubMedGoogle Scholar
  22. 22.
    Aronsson A, Tegner E (1983) Behçet’s syndrome in two brothers. Acta Derm Venereol 63:73–74PubMedGoogle Scholar
  23. 23.
    Fresko I, Soy M, Hamuryudan V et al (1998) Genetic anticipation in Behçet’s syndrome. Ann Rheum Dis 57:45–48PubMedCrossRefGoogle Scholar
  24. 24.
    Hamuryudan V, Yurdakul S, Ozbakir F et al (1991) Monozygotic twins concordant for Behçet’s syndrome. Arthritis Rheum 34:1071–1072PubMedCrossRefGoogle Scholar
  25. 25.
    Gül A, Inanç M, Ocal L et al (1997) HLA-B51 negative monozygotic twins discordant for Behçet’s disease. Br J Rheumatol 36:922–923PubMedCrossRefGoogle Scholar
  26. 26.
    Kobayashi T, Sudo Y, Okamura S et al (2005) Monozygotic twins concordant for intestinal Behçet’s disease. J Gastroenterol 40:421–425PubMedCrossRefGoogle Scholar
  27. 27.
    Verity DH, Marr JE, Ohno S et al (1999) Behçet’s disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens 54:213–220PubMedCrossRefGoogle Scholar
  28. 28.
    Ohno S, Ohguchi M, Hirose S et al (1982) Close association of HLA-Bw51 with Behçet’s disease. Arch Ophthalmol 100:1455–1458PubMedCrossRefGoogle Scholar
  29. 29.
    Ono S, Aoki K, Sugiura S et al (1973) HL-A5 and Behçet’s disease. Lancet 2:1383–1384PubMedCrossRefGoogle Scholar
  30. 30.
    Ono S, Nakayama E, Sugiura S et al (1975) Specific histocompatibility antigens associated with Behçet’s disease. Am J Ophthalmol 80:636–641PubMedGoogle Scholar
  31. 31.
    Kilmartin DJ, Finch A, Acheson RW (1997) Primary association of HLA-B51 with Behçet’s disease in Ireland. Br J Ophthalmol 81:649–653PubMedCrossRefGoogle Scholar
  32. 32.
    Ambresin A, Tran T, Spertini F, Herbort C (2002) Behçet’s disease in Western Switzerland: epidemiology and analysis of ocular involvement. Ocul Immunol Inflamm 10:53–63PubMedCrossRefGoogle Scholar
  33. 33.
    Pipitone N, Boiardi L, Olivieri I et al (2004) Clinical manifestations of Behçet’s disease in 137 Italian patients: results of a multicenter study. Clin Exp Rheumatol 22(Suppl 36):S46–S51PubMedGoogle Scholar
  34. 34.
    Bettencourt A, Pereira C, Carvalho L et al (2008) New insights of HLA class I association to Behçet’s disease in Portuguese patients. Tissue Antigens 72:379–382PubMedCrossRefGoogle Scholar
  35. 35.
    Sano K, Yabuki K, Imagawa Y et al (2001) The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet’s disease. Tissue Antigens 58:77–82PubMedCrossRefGoogle Scholar
  36. 36.
    Takemoto Y, Naruse T, Namba K et al (2008) Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet’s disease. Tissue Antigens 72:347–353PubMedCrossRefGoogle Scholar
  37. 37.
    Arber N, Klein T, Meiner Z et al (1991) Close association of HLA-B51 and B52 in Israeli patients with Behçet’s syndrome. Ann Rheum Dis 50:351–353PubMedCrossRefGoogle Scholar
  38. 38.
    Sugisaki K, Saito R, Takagi T et al (2005) HLA-B52-positive vasculo-Behçet’s disease: usefulness of magnetic resonance angiography, ultrasound study, and computed tomographic angiography for the early evaluation of multiarterial lesions. Mod Rheumatol 15:56–61PubMedCrossRefGoogle Scholar
  39. 39.
    Falk K, Rötzschke O, Takiguchi M et al (1995) Peptide motifs of HLA-B51, -B52 and -B78 molecules, and implications for Behçet’s disease. Int Immunol 7:223–228PubMedCrossRefGoogle Scholar
  40. 40.
    Sakaguchi T, Ibe M, Miwa K et al (1997) Predominant role of N-terminal residue of nonamer peptides in their binding to HLA-B* 5101 molecules. Immunogenetics 46:245–248PubMedCrossRefGoogle Scholar
  41. 41.
    Lemmel C, Rammensee H-G, Stevanovic S (2003) Peptide motif of HLA-B*5101 and the linkage to Behçet’s disease. In: Zierhut M, Ohno S (eds) Immunology of Behçet’s disease. Swets & Zeitlinger, Lisse, pp 127–137Google Scholar
  42. 42.
    Mizuki N, Inoko H, Ando H et al (1993) Behçet’s disease associated with one of the HLA-B51 subantigens, HLA-B* 5101. Am J Ophthalmol 116:406–409PubMedGoogle Scholar
  43. 43.
    Mizuki N, Ota M, Katsuyama Y et al (2002) Sequencing-based typing of HLA-B*51 alleles and the significant association of HLA-B*5101 and -B*5108 with Behçet’s disease in Greek patients. Tissue Antigens 59:118–121PubMedCrossRefGoogle Scholar
  44. 44.
    Pirim I, Atasoy M, Ikbal M et al (2004) HLA class I and class II genotyping in patients with Behçet’s disease: a regional study of eastern part of Turkey. Tissue Antigens 64:293–297PubMedCrossRefGoogle Scholar
  45. 45.
    Kera J, Mizuki N, Ota M et al (1999) Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet’s disease in Italian patients. Tissue Antigens 54:565–571PubMedCrossRefGoogle Scholar
  46. 46.
    Yabuki K, Ohno S, Mizuki N et al (1999) HLA class I and II typing of the patients with Behçet’s disease in Saudi Arabia. Tissue Antigens 54:273–277PubMedCrossRefGoogle Scholar
  47. 47.
    Yasuoka H, Okazaki Y, Kawakami Y et al (2004) Autoreactive CD8+ cytotoxic T lymphocytes to major histocompatibility complex class I chain-related gene A in patients with Behçet’s disease. Arthritis Rheum 50:3658–3662PubMedCrossRefGoogle Scholar
  48. 48.
    Martin MP, Gao X, Lee J-H et al (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31:429–434PubMedGoogle Scholar
  49. 49.
    Gül A, Uyar FA, Inanç M et al (2002) A weak association of HLA-B*2702 with Behçet’s disease. Genes Immun 3:368–372PubMedCrossRefGoogle Scholar
  50. 50.
    Duymaz-Tozkir J, Uyar A, Norman PJ et al (2008) Distribution of killer immunoglobulin-like receptor 3DL1/3DS1 alleles in Behçet’s disease. Arthritis Rheum 58(Suppl):S855Google Scholar
  51. 51.
    Wildner G, Thurau SR (1994) Cross-reactivity between an HLA-B27-derived peptide and a retinal autoantigen peptide: a clue to major histocompatibility complex association with autoimmune disease. Eur J Immunol 24:2579–2585PubMedCrossRefGoogle Scholar
  52. 52.
    Kurhan-Yavuz S, Direskeneli H, Bozkurt N et al (2000) Anti-MHC autoimmunity in Behçet’s disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis. Clin Exp Immunol 120:162–166PubMedCrossRefGoogle Scholar
  53. 53.
    Hill A, Takiguchi M, McMichael A (1993) Different rates of HLA class I molecule assembly which are determined by amino acid sequence in the alpha 2 domain. Immunogenetics 37:95–101PubMedCrossRefGoogle Scholar
  54. 54.
    Turner MJ, Sowders DP, DeLay ML et al (2005) HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 175:2438–2448PubMedGoogle Scholar
  55. 55.
    Takeno M, Kariyone A, Yamashita N et al (1995) Excessive function of peripheral blood neutrophils from patients with Behçet’s disease and from HLA-B51 transgenic mice. Arthritis Rheum 38:426–433PubMedCrossRefGoogle Scholar
  56. 56.
    Sensi A, Gavioli R, Spisani S et al (1991) HLA B51 antigen associated with neutrophil hyper-reactivity. Dis Markers 9:327–331PubMedGoogle Scholar
  57. 57.
    Taurog JD, Maika SD, Satumtira N et al (1999) Inflammatory disease in HLA-B27 transgenic rats. Immunol Rev 169:209–223PubMedCrossRefGoogle Scholar
  58. 58.
    Gül A, Hajeer AH, Worthington J et al (2001) Evidence for linkage of the HLA-B locus in Behçet’s disease, obtained using the transmission disequilibrium test. Arthritis Rheum 44(1):239–240PubMedCrossRefGoogle Scholar
  59. 59.
    Miretti MM, Walsh EC, Ke X et al (2005) A high-resolution linkage-disequilibrium map of the human major histocompatibility complex and first generation of tag single-nucleotide polymorphisms. Am J Hum Genet 76:634–646PubMedCrossRefGoogle Scholar
  60. 60.
    Mizuki N, Ota M, Kimura M et al (1997) Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet’s disease. Proc Natl Acad Sci U S A 94:1298–1303PubMedCrossRefGoogle Scholar
  61. 61.
    Hughes EH, Collins RW, Kondeatis E et al (2005) Associations of major histocompatibility complex class I chain-related molecule polymorphisms with Behçet’s disease in Caucasian patients. Tissue Antigens 66:195–199PubMedCrossRefGoogle Scholar
  62. 62.
    Mizuki N, Meguro A, Tohnai I et al (2007) Association of major histocompatibility complex Class I chain-related Gene A and HLA-B alleles with Behçet’s disease in Turkey. Jpn J Ophthalmol 51:431–436PubMedCrossRefGoogle Scholar
  63. 63.
    Mizuki N, Ota M, Yabuki K et al (2000) Localization of the pathogenic gene of Behçet’s disease by microsatellite analysis of three different populations. Invest Ophthalmol Vis Sci 41:3702–3708PubMedGoogle Scholar
  64. 64.
    Mizuki N, Ohno S, Tanaka H et al (1992) Association of HLA-B51 and lack of association of class II alleles with Behçet’s disease. Tissue Antigens 40:22–30PubMedCrossRefGoogle Scholar
  65. 65.
    Mizuki N, Ohno S, Ando H et al (1996) HLA-C genotyping of patient with Behçet’s disease in the Japanese population. Hum Immunol 50:47–53PubMedCrossRefGoogle Scholar
  66. 66.
    Sanz L, González-Escribano F, de Pablo R et al (1998) HLA-Cw*1602: a new susceptibility marker of Behçet’s disease in southern Spain. Tissue Antigens 51:111–114PubMedCrossRefGoogle Scholar
  67. 67.
    Park KS, Park JS, Nam JH et al (2007) HLA-E*0101 and HLA-G*010101 reduce the risk of Behçet’s disease. Tissue Antigens 69:139–144PubMedCrossRefGoogle Scholar
  68. 68.
    Meguro A, Inoko H, Ota M, et al (2009) Genetics of Behçet’s disease inside and outside the MHC. Ann Rheum Dis 69:747–754PubMedCrossRefGoogle Scholar
  69. 69.
    Ahmad T, Wallace GR, James T et al (2003) Mapping the HLA association in Behçet’s disease: a role for tumor necrosis factor polymorphisms? Arthritis Rheum 48:807–813PubMedCrossRefGoogle Scholar
  70. 70.
    Akman A, Sallakci N, Coskun M et al (2006) TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behçet’s disease. Br J Dermatol 155:350–356PubMedCrossRefGoogle Scholar
  71. 71.
    Park K, Kim N, Nam J et al (2006) Association of TNFA promoter region haplotype in Behçet’s disease. J Korean Med Sci 21:596–601PubMedCrossRefGoogle Scholar
  72. 72.
    Kamoun M, Chelbi H, Houman MH et al (2007) Tumor necrosis factor gene polymorphisms in Tunisian patients with Behçet’s disease. Hum Immunol 68:201–205PubMedCrossRefGoogle Scholar
  73. 73.
    Karasneh J, Hajeer AH, Barrett J et al (2003) Association of specific interleukin 1 gene cluster polymorphisms with increased susceptibility for Behçet’s disease. Rheumatology (Oxford) 42:860–864CrossRefGoogle Scholar
  74. 74.
    Chang HK, Jang WC, Park SB et al (2005) Association between interleukin 6 gene polymorphisms and Behçet’s disease in Korean people. Ann Rheum Dis 64:339–340PubMedCrossRefGoogle Scholar
  75. 75.
    Lee EB, Kim JY, Zhao J et al (2007) Haplotype association of IL-8 gene with Behçet’s disease. Tissue Antigens 69:128–132PubMedCrossRefGoogle Scholar
  76. 76.
    Wallace GR, Kondeatis E, Vaughan RW et al (2007) IL-10 genotype analysis in patients with Behçet’s disease. Hum Immunol 68:122–127PubMedCrossRefGoogle Scholar
  77. 77.
    Yanagihori H, Oyama N, Nakamura K et al (2006) Role of IL-12B promoter polymorphism in Adamantiades-Behçet’s disease susceptibility: an involvement of Th1 immunoreactivity against Streptococcus Sanguinis antigen. J Invest Dermatol 126:1534–1540PubMedCrossRefGoogle Scholar
  78. 78.
    Jang WC, Nam YH, Ahn YC et al (2008) Interleukin-17F gene polymorphisms in Korean patients with Behçet’s disease. Rheumatol Int 29:173–178PubMedCrossRefGoogle Scholar
  79. 79.
    Lee YJ, Kang SW, Park JJ et al (2006) Interleukin-18 promoter polymorphisms in patients with Behçet’s disease. Hum Immunol 67:812–818PubMedCrossRefGoogle Scholar
  80. 80.
    Mojtahedi Z, Ahmadi SB, Razmkhah M et al (2006) Association of chemokine receptor 5 (CCR5) delta32 mutation with Behçet’s disease is dependent on gender in Iranian patients. Clin Exp Rheumatol 24(Suppl 42):S91–S94PubMedGoogle Scholar
  81. 81.
    Ateş O, Dalyan L, Hatemi G et al (2009) Genetic susceptibility to Behçet’s syndrome is associated with NRAMP1 (SLC11A1) polymorphism in Turkish patients. Rheumatol Int 29:787–791PubMedCrossRefGoogle Scholar
  82. 82.
    Kim SK, Jang WC, Park SB et al (2006) SLC11A1 gene polymorphisms in Korean patients with Behçet’s disease. Scand J Rheumatol 35:398–401PubMedCrossRefGoogle Scholar
  83. 83.
    Ben Dhifallah I, Chelbi H, Braham A et al (2009) CTLA-4 +49A/G polymorphism is associated with Behçet’s disease in a Tunisian population. Tissue Antigens 73(3):213–217PubMedCrossRefGoogle Scholar
  84. 84.
    Park KS, Baek JA, Do JE et al (2009) CTLA4 gene polymorphisms and soluble CTLA4 protein in Behçet’s disease. Tissue Antigens 74:222–227PubMedCrossRefGoogle Scholar
  85. 85.
    Wang H, Nakamura K, Inoue T et al (2004) Mannose-binding lectin polymorphisms in patients with Behçet’s disease. J Dermatol Sci 36:115–117PubMedCrossRefGoogle Scholar
  86. 86.
    Park KS, Min K, Nam JH et al (2005) Association of HYPA haplotype in the mannose-binding lectin gene-2 with Behçet’s disease. Tissue Antigens 65:260–265PubMedCrossRefGoogle Scholar
  87. 87.
    Chen X, Katoh Y, Nakamura K et al (2006) Single nucleotide polymorphisms of Ficolin 2 gene in Behçet’s disease. J Dermatol Sci 43:201–205PubMedCrossRefGoogle Scholar
  88. 88.
    Hou S, Yang P, Du L et al (2008) SUMO4 gene polymorphisms in Chinese Han patients with Behçet’s disease. Clin Immunol 129:170–175PubMedCrossRefGoogle Scholar
  89. 89.
    Li K, Zhao M, Hou S, Du L et al (2008) Association between polymorphisms of FCRL3, a non-HLA gene, and Behçet’s disease in a Chinese population with ophthalmic manifestations. Mol Vis 14:2136–2142PubMedGoogle Scholar
  90. 90.
    Seo J, Park JS, Nam JH et al (2007) Association of CD94/NKG2A, CD94/NKG2C, and its ligand HLA-E polymorphisms with Behçet’s disease. Tissue Antigens 70:307–313PubMedCrossRefGoogle Scholar
  91. 91.
    Baranathan V, Stanford MR, Vaughan RW et al (2007) The association of the PTPN22 620W polymorphism with Behçet’s disease. Ann Rheum Dis 66:1531–1533PubMedCrossRefGoogle Scholar
  92. 92.
    Gunesacar R, Erken E, Bozkurt B et al (2007) Analysis of CD28 and CTLA-4 gene polymorphisms in Turkish patients with Behçet’s disease. Int J Immunogenet 34:45–49PubMedCrossRefGoogle Scholar
  93. 93.
    Meguro A, Ota M, Katsuyama Y et al (2008) Association of the toll-like receptor 4 gene polymorphisms with Behçet’s disease. Ann Rheum Dis 67:725–727PubMedCrossRefGoogle Scholar
  94. 94.
    Horie Y, Meguro A, Ota M et al (2009) Association of TLR4 polymorphisms with Behçet’s disease in a Korean population. Rheumatology (Oxford) 48:638–642CrossRefGoogle Scholar
  95. 95.
    Touitou I, Magne X, Molinari N et al (2000) MEFV mutations in Behçet’s disease. Hum Mutat 16:271–272PubMedCrossRefGoogle Scholar
  96. 96.
    Atagunduz P, Ergun T, Direskeneli H (2003) MEFV mutations are increased in Behçet’s disease (BD) and are associated with vascular involvement. Clin Exp Rheumatol 21(Suppl 30):S35–S37PubMedGoogle Scholar
  97. 97.
    Imirzalioglu N, Dursun A, Tastan B et al (2005) MEFV gene is a probable susceptibility gene for Behçet’s disease. Scand J Rheumatol 34:56–58PubMedCrossRefGoogle Scholar
  98. 98.
    Rabinovich E, Shinar Y, Leiba M et al (2007) Common FMF alleles may predispose to development of Behçet’s disease with increased risk for venous thrombosis. Scand J Rheumatol 36:48–52PubMedCrossRefGoogle Scholar
  99. 99.
    Ayesh S, Abu-Rmaileh H, Nassar S et al (2008) Molecular analysis of MEFV gene mutations among Palestinian patients with Behçet’s disease. Scand J Rheumatol 37:370–374PubMedCrossRefGoogle Scholar
  100. 100.
    Amoura Z, Dodé C, Hue S et al (2005) Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet’s disease. Arthritis Rheum 52:608–611PubMedCrossRefGoogle Scholar
  101. 101.
    Verity DH, Vaughan RW, Kondeatis E et al (2000) Intercellular adhesion molecule-1 gene polymorphisms in Behçet’s disease. Eur J Immunogenet 27:73–76PubMedCrossRefGoogle Scholar
  102. 102.
    Boiardi L, Salvarani C, Casali B et al (2001) Intercellular adhesion molecule-1 gene polymorphisms in Behçet’s disease. J Rheumatol 28:1283–1287PubMedGoogle Scholar
  103. 103.
    Kim EH, Mok JW, Bang DS et al (2003) Intercellular adhesion molecule-1 polymorphisms in Korean patients with Behçet’s disease. J Korean Med Sci 18:415–418PubMedCrossRefGoogle Scholar
  104. 104.
    Chmaisse HN, Fakhoury HA, Salti NN, Makki RF (2006) The ICAM-1 469 T/C gene polymorphism but not 241 G/A is associated with Behçet’s disease in the Lebanese population. Saudi Med J 27:604–607PubMedGoogle Scholar
  105. 105.
    Salvarani C, Boiardi L, Casali B et al (2002) Endothelial nitric oxide synthase gene polymorphisms in Behçet’s disease. J Rheumatol 29:535–540PubMedGoogle Scholar
  106. 106.
    Kim JU, Chang HK, Lee SS et al (2003) Endothelial nitric oxide synthase gene polymorphisms in Behçet’s disease and rheumatic diseases with vasculitis. Ann Rheum Dis 62:1083–1087PubMedCrossRefGoogle Scholar
  107. 107.
    Karasneh JA, Hajeer AH, Silman A et al (2005) Polymorphisms in the endothelial nitric oxide synthase gene are associated with Behçet’s disease. Rheumatology (Oxford) 44:614–617CrossRefGoogle Scholar
  108. 108.
    Ben Dhifallah I, Houman H, Khanfir M, Hamzaoui K (2008) Endothelial nitric oxide synthase gene polymorphism is associated with Behçet’s disease in Tunisian population. Hum Immunol 69:661–665PubMedCrossRefGoogle Scholar
  109. 109.
    Gül A, Ozbek U, Oztürk C et al (1996) Coagulation factor V gene mutation increases the risk of venous thrombosis in Behçet’s disease. Br J Rheumatol 35:1178–1180PubMedCrossRefGoogle Scholar
  110. 110.
    Verity DH, Vaughan RW, Madanat W et al (1999) Factor V Leiden mutation is associated with ocular involvement in Behçet’s disease. Am J Ophthalmol 128(3):352–356PubMedCrossRefGoogle Scholar
  111. 111.
    Mammo L, Al-Dalaan A, Bahabri SS, Saour JN (1997) Association of factor V Leiden with Behçet’s disease. J Rheumatol 24:2196–2198PubMedGoogle Scholar
  112. 112.
    Gül A, Aslantas AB, Tekinay T et al (1999) Procoagulant mutations and venous thrombosis in Behçet’s disease. Rheumatology (Oxford) 38:1298–1299CrossRefGoogle Scholar
  113. 113.
    Ricart JM, Vayá A, Todolí J et al (2006) Thrombophilic risk factors and homocysteine levels in Behçet’s disease in eastern Spain and their association with thrombotic events. Thromb Haemost 95(4):618–624PubMedGoogle Scholar
  114. 114.
    Nakao K, Isashiki Y, Sonoda S et al (2007) Nitric oxide synthase and superoxide dismutase gene polymorphisms in Behçet’s disease. Arch Ophthalmol 125:246–251PubMedCrossRefGoogle Scholar
  115. 115.
    Tursen U, Tamer L, Api H et al (2007) Cytochrome P450 polymorphisms in patients with Behçet’s disease. Int J Dermatol 46:153–156PubMedCrossRefGoogle Scholar
  116. 116.
    Yen JH, Tsai WC, Lin CH et al (2004) Cytochrome P450 1A1 and manganese superoxide dismutase gene polymorphisms in Behçet’s disease. J Rheumatol 31:736–740PubMedGoogle Scholar
  117. 117.
    Tamer L, Tursen U, Eskandari G et al (2005) N-acetyltransferase 2 polymorphisms in patients with Behçet’s disease. Clin Exp Dermatol 30:56–60PubMedCrossRefGoogle Scholar
  118. 118.
    Karasneh J, Gül A, Ollier WE et al (2005) Whole-genome screening for susceptibility genes in multicase families with Behçet’s disease. Arthritis Rheum 52:1836–1842PubMedCrossRefGoogle Scholar
  119. 119.
    Gül A, Hajeer AH, Worthington J et al (2001) Linkage mapping of a novel susceptibility locus for Behçet’s disease to chromosome 6p22-23. Arthritis Rheum 44:2693–2696PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Rheumatology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations