Genetic association study of Behcet's disease in multiple ethnic groups

• Project/Area Number: 22390065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Yokohama City University
• Principal Investigator: MIZUKI Nobuhisa 横浜市立大学, 医学研究科, 教授 (90336579)
• Co-Investigator(Kenkyū-buntansha): OTA Masao 信州大学, 医学部, 准教授 (50115333) ; MEGURO Akira 横浜市立大学, 医学研究科, 特任講師 (60508802) ; KAWAGOE Tatsukata 横浜市立大学, 医学部, 助教 (20564800)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2010: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: ゲノム医科学 / ゲノム / 遺伝子 / ベーチェット病 / 多因子性遺伝疾患

Research Abstract

To identify the susceptibility genes for Behcet’ s disease, we conducted a genome-wide association study in a Japanese population and replication studies in Turkish and Korean populations. We identified two new susceptibility loci, IL23R-IL12RB2 and IL10, for Behcet’ s disease. In addition, we identified further new loci for the disease by re-assessing the GWAS data.

Research Products

• [Journal Article] Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease (2013)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Ann Rheum Dis
  • URL: http://ard.bmj.com/content/early/2013/02/24/annrheumdis-2011-200288.long
  • Peer Reviewed
• [Journal Article] Staining internal limiting membrane with a mixture of BBG and sodium hyaluronate (2013)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Br J Ophthalmol Volume: 97 Issue: 6 Pages: 690-3
  • DOI: 10.1136/bjophthalmol-2012-302289
  • Peer Reviewed
• [Journal Article] A case of corneal endotheliitis with mumps virus RNA in aqueous humor detected by rt-PCR (2013)
  • Author(s): Mizuki N
  • Journal Title: Ocul Immunol Inflamm. Volume: 21 Issue: 2 Pages: 150-2
  • DOI: 10.3109/09273948.2012.747619
  • Peer Reviewed
• [Journal Article] Acute retinal necrosis: factors associated with anatomic and visual outcomes. (2013)
  • Author(s): Mizuki N
  • Journal Title: Jpn J Ophthalmol Volume: 57 Issue: 1 Pages: 98-103
  • DOI: 10.1007/s10384-012-0211-y
  • NAID: 10031168363
  • Peer Reviewed
• [Journal Article] Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behcet disease. (2013)
  • Author(s): Kirino Y
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Investigation of the Association Between Toll-like Receptor 9 Gene Polymorphisms and Sarcoidosis in Japanese Patients. (2013)
  • Author(s): Yotsumoto S
  • Journal Title: Ocular Immunology and Inflammation Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population. (2013)
  • Author(s): Mikami T
  • Journal Title: Molecular Vision Volume: 19 Pages: 845-851
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease. (2013)
  • Author(s): Lee YJ
  • Journal Title: Annals of the Rheumatic Diseases Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1 (2012)
  • Author(s): Mizuki N, Meguro A
  • Journal Title: Nat Genet Volume: 45 Issue: 2 Pages: 202-7
  • DOI: 10.1038/ng.2520
  • Peer Reviewed
• [Journal Article] Modification of Swan-Jacobs lens for iridocorneal angle surgery (2012)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Graefes Arch Clin Exp Ophthalmol
  • URL: http://link.springer.com/article/10.1007%2Fs00417-012-2232-0
  • Peer Reviewed
• [Journal Article] Modulation of human visual evoked potentials in 3-dimensional perception after stimuli produced with an integral imaging method (2012)
  • Author(s): Mizuki N
  • Journal Title: Clin EEG Neurosci Volume: 43 Issue: 4 Pages: 303-11
  • DOI: 10.1177/1550059412445608
  • Peer Reviewed
• [Journal Article] Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles (2012)
  • Author(s): Ota M, Meguro A, Kawagoe T, Mizuki N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Issue: 11 Pages: 7109-15
  • DOI: 10.1167/iovs.12-10491
  • Peer Reviewed
• [Journal Article] Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina (2012)
  • Author(s): Meguro A, Ota M, Kawagoe T, Mizuki N
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: e39300-e39300
  • DOI: 10.1371/journal.pone.0039300
  • Peer Reviewed
• [Journal Article] Genetic variants on chromosome 1q41 influence ocular axial length and high myopia (2012)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: PLoS Genet Volume: 8 Issue: 6 Pages: e1002753-e1002753
  • DOI: 10.1371/journal.pgen.1002753
  • Peer Reviewed
• [Journal Article] Immediate removal of posteriorly dislocated lens fragments through sclerocorneal incision during cataract surgery (2012)
  • Author(s): Kawagoe T, Mizuki N
  • Journal Title: Br J Ophthalmol Volume: 96 Issue: 8 Pages: 1058-62
  • DOI: 10.1136/bjophthalmol-2011-300864
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients (2012)
  • Author(s): Meguro A, Mizuki N
  • Journal Title: Mol Vis Volume: 18 Pages: 512-8
  • URL: http://www.molvis.org/molvis/v18/a56/
  • Peer Reviewed
• [Journal Article] Infliximab monotherapy versus infliximab and colchicine combination therapy in patients with Behcet's disease (2012)
  • Author(s): Kawagoe T, Mizuki N
  • Journal Title: Ocul Immunol Inflamm Volume: 20 Issue: 3 Pages: 193-7
  • DOI: 10.3109/09273948.2012.665124
  • Peer Reviewed
• [Journal Article] Confirmation of TBK1 duplication in normal tension glaucoma (2012)
  • Author(s): Kawase K, et al
  • Journal Title: Experimental Eye Research Volume: 96 Issue: 1 Pages: 178-180
  • DOI: 10.1016/j.exer.2011.12.021
  • Peer Reviewed
• [Journal Article] Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population (2012)
  • Author(s): Horie Y, et al
  • Journal Title: Rheumatology Volume: (印刷中) Issue: 6 Pages: 983-6
  • DOI: 10.1093/rheumatology/ker444
  • Peer Reviewed
• [Journal Article] Thermocautery for inferior conjunctivochalasis (2012)
  • Author(s): Mizuki N
  • Journal Title: Cornea Volume: 31 Issue: 5 Pages: 514-9
  • DOI: 10.1097/ico.0b013e3181dc81d2
  • Peer Reviewed
• [Journal Article] Cyclooxygenase inhibitor improved an exudative lesion of choroidal neovascularization in age-related macular degeneration (2012)
  • Author(s): Mizuki N
  • Journal Title: Eur J Ophthalmol Volume: 22 Pages: 495-8
  • Peer Reviewed
• [Journal Article] Anatomical and functional changes of retina following subretinal injection of high-speed fluid (2012)
  • Author(s): Uemoto R, et al
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: 250 Issue: 3 Pages: 447-450
  • DOI: 10.1007/s00417-011-1800-z
  • Peer Reviewed
• [Journal Article] Factors associated with enlargement of chorioretinal atrophy after intravitreal bevacizumab for myopic choroidal neovascularization (2012)
  • Author(s): Uemoto R, et al
  • Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology Volume: (印刷中) Issue: 7 Pages: 989-97
  • DOI: 10.1007/s00417-011-1921-4
  • Peer Reviewed
• [Journal Article] The carboxyl-terminal region of Crtac1B/LOTUS acts as a functional domain in endogenous antagonism to Nogo receptor-1 (2012)
  • Author(s): Mizuki N
  • Journal Title: Biochem Biophys Res Commun Volume: 418 Issue: 2 Pages: 390-5
  • DOI: 10.1016/j.bbrc.2012.01.033
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients. (2012)
  • Author(s): Sakuyama K
  • Journal Title: Molecular Vision Volume: 18 Pages: 512-518
  • Peer Reviewed
• [Journal Article] Lack of association between IL10 polymorphisms and sarcoidosis in Japanese patients (2012)
  • Author(s): Sakuyama K, et al
  • Journal Title: Molecular Vision Volume: 18 Pages: 512-518
  • Peer Reviewed
• [Journal Article] Sarcoidosis (2011)
  • Author(s): Kawagoe T.Mizuki N
  • Journal Title: Curr Opin Ophthalmol Volume: 22 Issue: 6 Pages: 502-7
  • DOI: 10.1097/icu.0b013e32834bbd7e
  • Peer Reviewed
• [Journal Article] Clinical Course before and after Cataract and Glaucoma Surgery under Systemic Infliximab Therapy in Patients with Behcet's Disease (2011)
  • Author(s): Mizuki N
  • Journal Title: Case Rep Ophthalmol Volume: 2 Issue: 2 Pages: 189-92
  • DOI: 10.1159/000329190
  • Peer Reviewed
• [Journal Article] Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients (2011)
  • Author(s): Ito Ryuta; Ota Masao; Meguro Akira, et al
  • Journal Title: OCULAR IMMUNOLOGY AND INFLAMMATION Volume: 19:3 Issue: 3 Pages: 202-205
  • DOI: 10.3109/09273948.2011.553981
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma (2011)
  • Author(s): Meguro A, Ota M, Mizuki N
  • Journal Title: Mol Vis Volume: 17 Pages: 792-6
  • URL: http://www.molvis.org/molvis/v17/a89/
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese population (2011)
  • Author(s): Kawagoe T, Meguro A, Ota M, Mizuki N
  • Journal Title: Mol Vis Volume: 17 Pages: 731-6
  • URL: http://www.molvis.org/molvis/v17/a83/
  • Peer Reviewed
• [Journal Article] Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis (2011)
  • Author(s): Mizuki N
  • Journal Title: J Hum Genet Volume: 56 Issue: 3 Pages: 196-9
  • DOI: 10.1038/jhg.2010.159
  • NAID: 10030658234
  • Peer Reviewed
• [Journal Article] Association analysis of Toll-like receptor 7 gene polymorphisms and Behcet's disease in Japanese (2011)
  • Author(s): Sada T, et al
  • Journal Title: Human Immunology Volume: 72 Issue: 3 Pages: 269-272
  • DOI: 10.1016/j.humimm.2010.12.007
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma (2011)
  • Author(s): Yasumura R, et al
  • Journal Title: Molecular Vision Volume: 17 Pages: 792-796
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese (2011)
  • Author(s): Sato M, et al
  • Journal Title: Molecular Vision Volume: 17 Pages: 731-736
  • Peer Reviewed
• [Journal Article] Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma. (2011)
  • Author(s): Yasumura R, et al
  • Journal Title: Mol Vis Volume: 17 Pages: 792-796
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 (TLR2) gene polymorphisms are not associated with sarcoidosis in the Japanese. (2011)
  • Author(s): Sato M, et al
  • Journal Title: Mol Vis Volume: 17 Pages: 731-736
  • Peer Reviewed
• [Journal Article] Association analysis of Toll-like receptor 7 gene polymorphisms and Behcet's disease in Japanese. (2011)
  • Author(s): Sada T, et al
  • Journal Title: Hum Immunol Volume: 72 Pages: 269-272
  • Peer Reviewed
• [Journal Article] Treatment of pterygium by ligation and bevacizumab injection (2010)
  • Author(s): Mizuki N
  • Journal Title: Cornea Volume: 31 Issue: 11 Pages: 1339-41
  • DOI: 10.1097/ico.0b013e3182408bc7
  • Peer Reviewed
• [Journal Article] Genotyping HLA-DRB1 and HLA-DQB1 alleles in Japanese patients with normal tension glaucoma (2010)
  • Author(s): Meguro A, Ota M, Mizuki N
  • Journal Title: Mol Vis Volume: 16 Pages: 1874-9
  • URL: http://www.molvis.org/molvis/v16/a203/
  • Peer Reviewed
• [Journal Article] TRIM39 and RNF39 are associated with Behcet's disease independently of HLA-B*51 and ?A*26 (2010)
  • Author(s): Kurata R, Nakaoka H, Tajima A, Hosomichi K, Shiina T, Meguro A, Mizuki N, Ohono S, Inoue I, InokoH
  • Journal Title: Biochem Biophys Res Commun Volume: 401 Issue: 4 Pages: 533-537
  • DOI: 10.1016/j.bbrc.2010.09.088
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid suppresses ocular inflammation in endotoxin-induced uveitis (2010)
  • Author(s): Mizuki N
  • Journal Title: Mol Vis Volume: 16 Pages: 1382-8
  • NAID: 120002386831
  • URL: http://www.molvis.org/molvis/v16/a152/
  • Peer Reviewed
• [Journal Article] Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci (2010)
  • Author(s): Mizuki N, Meguro A, Ota M, Kawagoe T
  • Journal Title: Nat Genet Volume: 42 Issue: 8 Pages: 703-6
  • DOI: 10.1038/ng.624
  • Peer Reviewed
• [Journal Article] Natural killer cells control a T-helper 1 response in patients with Behcet's disease (2010)
  • Author(s): Mizuki N
  • Journal Title: Arthritis Res Ther Volume: 12 Issue: 3
  • DOI: 10.1186/ar3005
  • Peer Reviewed
• [Journal Article] Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci. (2010)
  • Author(s): Mizuki N, et al
  • Journal Title: Nat Genet Volume: 42 Pages: 703-706
  • Peer Reviewed
• [Journal Article] Genetics of Behcet disease inside and outside the MHC. (2010)
  • Author(s): Meguro A, et al
  • Journal Title: Ann Rheum Dis Volume: 69 Pages: 747-754
  • Peer Reviewed
• [Journal Article] Genome-wide association study of normal tension glaucoma : common variants in SRBD1 and ELOVL5 contribute to disease susceptibility. (2010)
  • Author(s): Writing Committee for the Normal Tension Glaucoma Genetic Study Group of Japan Glaucoma Society
  • Journal Title: Ophthalmology Volume: 117 Pages: 1331-1338
  • Peer Reviewed
• [Journal Article] Genotyping HLA-DRB1 and HLA-DQB1 alleles in Japanese patients with normal tension glaucoma. (2010)
  • Author(s): Suzuki M, et al
  • Journal Title: Mol Vis Volume: 16 Pages: 1874-1879
  • Peer Reviewed
• [Journal Article] RIM39 and RNF39 are associated with Behcet's disease independently of HLA-B*51 and -A*26. (2010)
  • Author(s): Kurata R, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 401 Pages: 533-537
  • Peer Reviewed
• [Journal Article] Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma. (2010)
  • Author(s): Murakami K, et al
  • Journal Title: Mol Vis Volume: 16 Pages: 462-466
  • Peer Reviewed
• [Presentation] Genome-wide association studies on multifactorial ocular diseases (2011)
  • Author(s): Mizuki N
  • Organizer: 52nd Annual Meeting of Taiwan Ophthalmology Society
  • Place of Presentation: 台湾・台北(招待講演)
  • Year and Date: 2011-11-27
• [Presentation] Molecular Genetics of Behcet's disease (2011)
  • Author(s): Mizuki N, et al
  • Organizer: The 11th International Ocular Inflammation Society
  • Place of Presentation: インド・ゴア
  • Year and Date: 2011-11-14
• [Presentation] Behcet's disease : Role of regulatory T cells in disease remission (2011)
  • Author(s): Mizuki N, et al
  • Organizer: The 11th International Ocular Inflammation Society
  • Place of Presentation: インド・ゴア(招待講演)
  • Year and Date: 2011-11-14
• [Presentation] Contribution of the HLA-A region to genetic predisposition in Behcet's disease. (2010)
  • Author(s): Meguro A
  • Organizer: 14th International Conference on Behget's Diseas
  • Place of Presentation: イギリス・ロンドン(招待講演)
  • Year and Date: 2010-07-09