Novel genetic analysis in Behcet's disease

• Project/Area Number: 19592030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Yokohama City University
• Principal Investigator: NISHIDE Tadayuki Yokohama City University, 医学部, 助教 (90347344)
• Co-Investigator(Kenkyū-buntansha): MIZUKI Nobuhisa 横浜市立大学, 医学研究科, 教授 (90336579) ; ITO Norihiko 横浜市立大学, 医学部, 助教 (80264654) ; 大野 重昭 北海道大学, 大学院・医学研究科, 教授 (50002382) ; 猪子 英俊 東海大学, 医学部, 教授 (10101932)
• Co-Investigator(Renkei-kenkyūsha): OHNO Shigeaki 北海道大学, 大学院・医学研究科, 特任教授 (50002382) ; INOKO Hidetoshi 東海大学, 医学部, 教授 (10101932)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ゲノム / 遺伝子 / マイクロサテライト / SNP / 多因子性遺伝疾患 / トランスレーショナルリサーチ

Research Abstract

To identify susceptibility genes for Behcet's disease (BD), we performed a genome-wide association study of BD achieved through three rounds of pooled DNA screening using a comprehensive set 23,465 microsatellite markers in 300 Japanese cases and 300 controls, and identified the six best positively associated microsatellites with BD.

Research Products

• [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, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
  • Journal Title: Nature Genetics (in press)
• [Journal Article] Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma. (2010)
  • Author(s): Murakami K, Meguro A, Ota M, Shiota T, Nomura N, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, IwMurakami K, Meguro A, Ota M, Shi
  • Journal Title: Mol Vis 16 Pages: 462-466
• [Journal Article] Genetics of Behcet's disease inside and outside the MHC. (2010)
  • Author(s): Meguro A, Inoko H, Ota M, Katsuyama Y, Oka A, Okada E, Yamakawa R, Yuasa T, Fujioka T, Ohno S, Bahram S, Mizuki N
  • Journal Title: Ann Rheum Dis 69 Pages: 747-754
• [Journal Article] Genome-wide association study of normal tension glaucoma : common variants in SRBD1 and ELOVL5 contribute to disease susceptibility (2010)
  • Author(s): The NTG Genetic Study Group of Japan Glaucoma Society
  • Journal Title: Ophthalmology (in press)
  • Peer Reviewed
• [Journal Article] Genetics of Behcet's disease inside and outside the MHC (2010)
  • Author(s): Meguro A
  • Journal Title: Ann Rheum Dis 69 Pages: 747-754
  • Peer Reviewed
• [Journal Article] Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma (2010)
  • Author(s): Murakami K
  • Journal Title: Mol Vis 16 Pages: 462-466
  • Peer Reviewed
• [Journal Article] P1 and P2 components of human visual evoked potentials are modulated by depth perception of 3-dimensional images (2010)
  • Author(s): Omoto S
  • Journal Title: Clin Neurophysiol 121 Pages: 386-391
  • Peer Reviewed
• [Journal Article] Investigation of the association between TLR2 gene polymorphisms and Behcet's disease in Japanese patients. (2009)
  • Author(s): Tomiyama R, Meguro A, Ota M, Katsuyama Y, Nishide T, Uemoto R, Iijima Y, Ohno S, Inoko H, Mizuki N
  • Journal Title: Human Immunol 70(1) Pages: 41-44
• [Journal Article] Association of TLR4 polymorphisms with Behcet's disease in a Korean population. (2009)
  • Author(s): Horie Y, Meguro A, Ota M, Kitaichi N, Katsuyama Y, Takemoto Y, Namba K, Yoshida K, Song YW, Park KS, Lee EB, Inoko H, Mizuki N, Ohno S
  • Journal Title: Rheumatology 48(6) Pages: 638-642
• [Journal Article] Association of toll-like receptor 2 gene polymorphisms with normal tension glaucoma. (2009)
  • Author(s): Nakamura J, Meguro A, Ota M, Nomura E, Nishide T, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, INakamura J, Meguro A, Ota M, Nomu
  • Journal Title: Mol Vis 15 Pages: 2905-2910
• [Journal Article] Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan. (2009)
  • Author(s): Asukata Y, Ota M, Meguro A, Katsuyama Y, Ishihara M, Namba K, Kitaichi N, Morimoto S, Kaburaki T, Ando Y, Takenaka S, Inoko H, Ohno S, Mizuki N
  • Journal Title: Mol Vis 15 Pages: 2673-2682
• [Journal Article] New susceptibility locus for high myopia is linked to the uromodulin-like 1 (UMODL1) gene region on chromosome 21q22. 3. (2009)
  • Author(s): Nishizaki R, Ota M, Inoko H, Meguro A, Shiota T, Okada E, Mok J, Oka A, Ohno S, Mizuki N
  • Journal Title: Eye 23(1) Pages: 222-229
• [Journal Article] Investigation of the association between the GLC3A locus and normal tension glaucoma in Japanese patients by microsatellite analysis. (2009)
  • Author(s): Kamio Y, Meguro A, Ota M, Nomura N, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, Iwase A, Ohno SKamio Y, Meguro A
  • Journal Title: Clinical Ophthalmol 3 Pages: 183-188
• [Journal Article] Association of microsatellite polymorphisms of the GPDS1 locus with normal tension glaucoma in the Japanese population. (2009)
  • Author(s): Nakamura K, Ota M, Meguro A, Nomura N, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, Iwase A, OhnNakamura K, Ota M, Meg
  • Journal Title: Clinical Ophthalmol 3 Pages: 307-312
• [Journal Article] Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth (2009)
  • Author(s): Albuquerque RJ
  • Journal Title: Nature Medicine 15 Pages: 1023-1030
  • Peer Reviewed
• [Journal Article] Investigation of the association between TLR2 gene polymorphisms and Behcet's disease in Japanese patients (2009)
  • Author(s): Tomiyama R
  • Journal Title: Human Immunol 70 Pages: 41-44
  • Peer Reviewed
• [Journal Article] Association of toll-like receptor 2 gene polymorphisms with normal tension glaucoma (2009)
  • Author(s): Nakamura J
  • Journal Title: Mol Vis 15 Pages: 2905-2910
  • Peer Reviewed
• [Journal Article] Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan (2009)
  • Author(s): Asukata Y
  • Journal Title: Mol Vis 15 Pages: 2673-2682
  • Peer Reviewed
• [Journal Article] New susceptibility locus for high myopia is linked to the uromodulin -like 1 (UMODL1) gene region on chromosome 21q22.3 (2009)
  • Author(s): Nishizaki R
  • Journal Title: Eye 23 Pages: 222-229
  • Peer Reviewed
• [Journal Article] Association of TLR4 polymorphisms with Behcet's disease in a Korean population (2009)
  • Author(s): Horie Y
  • Journal Title: Human Immunol 70 Pages: 41-44
  • Peer Reviewed
• [Journal Article] Association of toll-like receptor 2 gene polymorphisms with normal tension glaucoma (2009)
  • Author(s): Nakamura J
  • Journal Title: Rheumatology 48 Pages: 638-642
  • Peer Reviewed
• [Journal Article] Investigation of the association between the GLC3A locus and normal tension glaucoma in Japanese patients by microsatellite analysis (2009)
  • Author(s): Kamio Y
  • Journal Title: Clinical Ophthalmol 3 Pages: 183-188
  • Peer Reviewed
• [Journal Article] Association of microsatellite polymorphisms of the GPDS1 locus with normal tension glaucoma in the Japanese population (2009)
  • Author(s): Nakamura K
  • Journal Title: Clinical Ophthalmol 3 Pages: 307-312
  • Peer Reviewed
• [Journal Article] New technique for inserting 27-gauge twinlight chandelier illumination fibers into the eye using intravenous cannula (2009)
  • Author(s): Uemoto R
  • Journal Title: Retina 29 Pages: 1040-1042
  • Peer Reviewed
• [Journal Article] Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients (2009)
  • Author(s): Horie Y
  • Journal Title: Mol Vis 15 Pages: 1115-1119
  • Peer Reviewed
• [Journal Article] Immunologic mechanisms of corneal allografts reconstituted from cultured allogeneic endothelial cells in an immune-privileged site (2009)
  • Author(s): Hayashi T
  • Journal Title: Invest Ophthalmol Vis Sci 50 Pages: 3151-3158
  • Peer Reviewed
• [Journal Article] New susceptibility locus for high myopia is linked to the uromodulin-like 1(UMODL1) gene region on chromosome 21q22.3 (2009)
  • Author(s): Nishizaki R
  • Journal Title: Eye 23 Pages: 222-229
  • Peer Reviewed
• [Journal Article] Investigation of association between TLR2 gene polymorphisms and Behcet's disease in Japanese patients (2009)
  • Author(s): Tomiyama R
  • Journal Title: Human Immunol 70 Pages: 41-44
  • Peer Reviewed
• [Journal Article] Investigation of the association between the GLC3A locus and normal tension glaucoma in Japanese patients by microsatellite analysis (2009)
  • Author(s): Kamio M
  • Journal Title: Clinical Ophthalmol 3 Pages: 183-188
  • Peer Reviewed
• [Journal Article] Association of toll-like receptor 4 gene polymorphisms with normal tension glaucoma. (2008)
  • Author(s): Shibuya E, Meguro A, Ota M, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Nishida T, Inatani M, Tanihara H, Aihara M, Araie M, Fukuchi T, Abe H, Higashide T, Sugiyama K, Kanamoto T, Kiuchi Y, Iwase A, Ohno S, Inoko Shibuya E
  • Journal Title: Invest Opthalmol Vis Sci 49(10) Pages: 4453-4457
• [Journal Article] Association of the toll-like receptor 4 gene polymorphisms with Behcet's disease. (2008)
  • Author(s): Meguro A, Ota M, Katsuyama Y, Oka A, Ohno S, Inoko H, Mizuki N
  • Journal Title: Ann Rheum Dis 67(5) Pages: 725-727
• [Journal Article] Four-digit allele genotyping of HLA-A and HLA-B genes in Japanese patients with Behcet's disease (BD) by a PCR-SSOP-luminex method and stratification analysis according to each major symptom of BD. (2008)
  • Author(s): Kamiishi T, Itoh Y, Meguro A, Nishida T, Sasaki S, Nanba K, Ohno S, Inoko H, Mizuki N
  • Journal Title: Nippon Ganka Gakkai Zasshi 112(5) Pages: 451-458
  • NAID: 10021292413
• [Journal Article] Association of the toll-like receptor 4 gene polymorphisms with Behcet's disease (2008)
  • Author(s): Meguro A
  • Journal Title: Ann Rheum Dis 67 Pages: 725-727
  • Peer Reviewed
• [Journal Article] Association of toll-like receptor 4 gene polymorphisms with normal tension glaucoma (2008)
  • Author(s): Shibuya E
  • Journal Title: Invest Opthalmol Vis Sci 49 Pages: 4453-4457
  • Peer Reviewed
• [Journal Article] Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma (2008)
  • Author(s): Akiyama M
  • Journal Title: Br J Opthalmol 192 Pages: 1293-1296
  • Peer Reviewed
• [Journal Article] Rac1 mediates phorbol 12-myristate 13-acetate-induced migration of glioblastoma cells via paxillin (2008)
  • Author(s): Nomura N
  • Journal Title: Oncol Rep 20 Pages: 705-711
  • Peer Reviewed
• [Journal Article] Association of reduced HO-1 with excessive TLR4 expression in peripheral blood mononuclear cells of Behcet's disease (2008)
  • Author(s): Kirino Y
  • Journal Title: Arthritis Res Ther 10
  • Peer Reviewed
• [Journal Article] A mouse model of allogeneic corneal endothelial cell transplantation (2008)
  • Author(s): Hayashi T
  • Journal Title: Cornea 27 Pages: 699-705
  • Peer Reviewed
• [Journal Article] Mutation screening of the CARD15 gene in sarcoidosis (2008)
  • Author(s): Akahoshi M
  • Journal Title: Tissue Antigens 71 Pages: 564-567
  • Peer Reviewed
• [Journal Article] Spontaneous closure of a macular hole caused by a ruptured retinal areterial macroaneurysm (2008)
  • Author(s): Uemoto R
  • Journal Title: Eur J Ophthalmol 18 Pages: 462-465
  • Peer Reviewed
• [Journal Article] Ultrasound biomicroscopic measurement of anterior chamber biometry between before and after pupil dilation in children (2008)
  • Author(s): Tsuchiya AK
  • Journal Title: Eur J Ophthalmol 18 Pages: 532-539
  • Peer Reviewed
• [Journal Article] Re evaluation of heterogeneity in HLA-B^*510101 associated with Behcet's disease (2008)
  • Author(s): Takemoto Y
  • Journal Title: Tissue Antigens 72 Pages: 347-363
  • Peer Reviewed
• [Journal Article] Preferential activation of circulating CD8^+ and gammadelta T cells in patients with active Behcet's disease and HLA-B51 (2008)
  • Author(s): Yasuoka H
  • Journal Title: Clin Exp Pheumatol 26
  • Peer Reviewed
• [Journal Article] Association of major histocompatibility complex class I chain-related gene A and HLA-B alleles with Behcet's disease in Turkey. (2007)
  • Author(s): Mizuki N, Meguro A, Tohnai I, Gul A, Ohno S, Mizuki N
  • Journal Title: Jpn J Ophthalmol 51(6) Pages: 431-436
  • NAID: 10020179012
• [Journal Article] A single nucleotide polymorphism analysis of the LAMA1 gene in Japanese patients with high myopia. (2007)
  • Author(s): Sasaki S, Ota M, Meguro A, Nishizaki R, Okada E, Mok J, Kimura T, Oka A, Katsuyama Y, Ohno S, Inoko H, Mizuki N
  • Journal Title: Clinical Opthalmol 1(3) Pages: 289-295
• [Journal Article] Lack of association with high myopia and the MYP2 locus in the Japanese population by high resolution microsatellite analysis on chromosome 18. (2007)
  • Author(s): Yamane T, Mok J, Oka A, Okada E, Nishizaki R, Meguro A, Yonemoto J, Kulski JK, Ohno S, Inoko H, Mizuki N
  • Journal Title: Clinical Opthalmol 1(3) Pages: 311-316
• [Journal Article] Association of major histocompatibility complex class I chain-related gene A and HLA-B alleles with Behcet's disease in Turkey (2007)
  • Author(s): Mizuki N
  • Journal Title: Jpn J Ophthalmol 51 Pages: 431-436
  • NAID: 10020179012
  • Peer Reviewed
• [Journal Article] MDR1 polymorphisms effect cyclosporine AUC0-4 values in Behcet's disease patients (2007)
  • Author(s): Katsuyama Y
  • Journal Title: Clin Ophthalmol 1 Pages: 297-303
  • Peer Reviewed
• [Journal Article] Lack of association of Toll-like receptor 9 gene polymorphism with Behcet's disease in Japanese patients (2007)
  • Author(s): Ito A
  • Journal Title: Tissue Antigens 70 Pages: 423-426
  • Peer Reviewed
• [Journal Article] High-resolution mapping for essential hypertension using microsat ellite markers (2007)
  • Author(s): Yatsu K
  • Journal Title: Hyperension 49 Pages: 446-452
  • Peer Reviewed
• [Journal Article] Microsatellite markers for genome-wide association studies (2007)
  • Author(s): Bahram S
  • Journal Title: Nature Reviews Genetics 8 Pages: 164-164
  • Peer Reviewed
• [Presentation] Molecular genetic studies on Behcet's disease in Japan. (2009)
  • Author(s): Meguro A, Mizuki N, Ohno S
  • Organizer: The 10th International Ocular Inflammation Society Congress
  • Place of Presentation: Praque, Czech Republic
• [Presentation] Whole genome association study on Behcet's disease. (2007)
  • Author(s): Meguro A, Mizuki N
  • Organizer: Japan and Korea Joint Meeting on Behcet's disease
  • Place of Presentation: Yokohama, Japan
• [Patent(Industrial Property Rights)] 正常眼圧緑内障疾患感受性遺伝子及びその利用 (2008)
  • Inventor(s): 水木信久
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 2008-302986
  • Filing Date: 2008-11-27