Studies on the genetic factors, environmental factors and their interactions towards the establishment of genome medicine of rheumatic diseases

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390271
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: TSUCHIYA Naoyuki University of Tsukuba, 大学院・人間総合科学研究科, 教授 (60231437)
• Co-Investigator(Kenkyū-buntansha): TOKUNAGA Katsushi 東京大学, 大学院・医学系研究科, 教授 (40163977) ; TSUTSUMI Akito 筑波大学, 大学院・人間総合科学研究科, 准教授 (60250453)
• Project Period (FY): 2007 – 2009
• Keywords: 全身性エリテマトーデス / 全身性強皮症 / 関節リウマチ / 疾患感受性遺伝子 / BLK / STAT4 / IRF5 / TNFAIP3 / TNIP1

Research Abstract

In this study, we confirmed association of IRF5, STAT4, BLK, TNFAIP3 and TNIP1 polymorphisms with systemic lupus erythematosus in Japanese. In addition, we found that the genetic contribution of BLK, STAT4 and TNIP1 is greater in Japanese than in Caucasians because of higher risk genotype frequencies. Moreover, we found that IRF5, STAT4 and BLK are also associated with systemic sclerosis, thereby establishing that these genes are shared susceptibility genes to multiple rheumatic diseases both in the Asian and Caucasian populations.

Research Products

• [Journal Article] Association of TNFAIP3 polymorphism with susceptibility to systemic lupus erythematosus in a Japanese population (2010)
  • Author(s): Kawasaki A, Ito I, Ito S, Hayashi T, Goto D, Matsumoto I, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N.
  • Journal Title: J Biomed Biotechnol
  • Peer Reviewed
• [Journal Article] Association of the FAM167A-BLK region with systemic sclerosis (2010)
  • Author(s): Ito I, Kawaguchi K, Kawasaki A, Hasegawa M, Ohashi J, Kawamoto M, Fujimoto M, Takehara K, Sato S, Hara M, Tsuchiya N.
  • Journal Title: Arthritis Rheum 62 Pages: 890-895
  • Peer Reviewed
• [Journal Article] Replication of association between FAM167A (C8orf13)-BLK region and rheumatoid arthritis in a Japanese population (2010)
  • Author(s): Ito I, Kawasaki A, Ito S, Kondo Y, Sugihara M, Horikoshi M, Hayashi T, Goto D, Matsumoto I, Tsutsumi A, Takasaki Y, Hashimoto H, Matsuta K, Sumida T, Tsuchiya N.
  • Journal Title: Ann Rheum Dis 69 Pages: 936-937
  • Peer Reviewed
• [Journal Article] Association of STAT4 polymorphism with systemic sclerosis in a Japanese population (2009)
  • Author(s): Tsuchiya N, Kawasaki A, Hasegawa M, Fujimoto M, Takehara K, Kawaguchi Y, Kawamoto M, Hara M, Sato S.
  • Journal Title: Ann Rheum Dis 68 Pages: 1375-1376
  • Peer Reviewed
• [Journal Article] Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population (2009)
  • Author(s): Ito I, Kawaguchi Y, Kawasaki A, Hasegawa M, Ohashi J, Hikami K, Kawamoto M, Fujimoto M, Takehara K, Sato S, Hara M, Tsuchiya N.
  • Journal Title: Arthritis Rheum 60 Pages: 1845-1850
  • Peer Reviewed
• [Journal Article] Association study of a polymorphism of the CTGF gene and susceptibility to systemic sclerosis in the Japanese population (2009)
  • Author(s): Kawaguchi Y, Ota Y, Kawamoto M, Ito I, Tsuchiya N, Sugiura T, Katsumata Y, Soejima M, Sato S, Hasegawa M, Fujimoto M, Takehara K, Kuwana M, Yamanaka H, Hara M.
  • Journal Title: Ann Rheum Dis 68 Pages: 1921-1924
  • Peer Reviewed
• [Journal Article] Combining effects of polymorphism of tumor necrosis factor α 5'-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis (2009)
  • Author(s): Ichikawa N, Kotake S, Hakoda M, Higami K, Kawasaki A, Furuya T, Nanke Y, Tsuchiya N, Tokunaga K, Kamatani N.
  • Journal Title: Mod Rheumatol 19 Pages: 134-139
  • Peer Reviewed
• [Journal Article] Replication of the association between C8orf13-BLK region and systemic lupus erythematosus in a Japanese population (2009)
  • Author(s): Ito I, Kawasaki A, Ito S, Hayashi T, Goto D, Matsumoto I, Tsutsumi A, Hom G, Graham RR, Takasaki Y, Hashimoto H, Ohashi J, Behrens TW, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Rheum 60 Pages: 553-558
  • Peer Reviewed
• [Journal Article] Role of IRF5, STAT4 and BLK polymorphisms for the genetic predisposition to systemic lupus erythematosus in Japanese (2009)
  • Author(s): Tsuchiya N, Kawasaki A, Ito I.
  • Journal Title: Inflammation Regenerat 29 Pages: 190-197
• [Journal Article] Anti-glucose-6-phosphate isomerase, anti-cyclic citrullinated peptide antibodies and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis (2008)
  • Author(s): Furuya T, Matsumoto I, Tsuchiya N, Hakoda M, Ichikawa N, Higami K, Nanke Y, Sumida T, Kamatani N, Kotake S.
  • Journal Title: Clin Exp Rheumatol 26 Pages: 918-921
  • Peer Reviewed
• [Journal Article] Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population : a case-control association study of the STAT1-STAT4 region (2008)
  • Author(s): Kawasaki A, Ito I, Hikami K, Ohashi J, Hayashi T, Goto D, Matsumoto I, Ito S, Tsutsumi A, Koga M, Arinami T, Graham RR, Hom G, Takasaki Y, Hashimoto H, Behrens TW, Sumida T, Tsuchiya N.
  • Journal Title: Arthritis Res Ther 10 Pages: R113
  • Peer Reviewed
• [Journal Article] Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis (2008)
  • Author(s): Hikami K, Ehara Y, Hasegawa M, Fujimoto M, Matsushita M, Oka T, Takehara K, Sato S, Tokunaga K, Tsuchiya N.
  • Journal Title: Biochem Biophys Res Commun 373 Pages: 403-407
  • Peer Reviewed
• [Journal Article] Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis (2008)
  • Author(s): Mamegano K, Kuroki K, Miyashita R, Kusaoi M, Kobayashi S, Matsuta K, Maenaka K, Colonna M, Ozaki S, Hashimoto H, Takasaki Y, Tokunaga K, Tsuchiya N.
  • Journal Title: Genes Immun 9 Pages: 214-223
  • Peer Reviewed
• [Journal Article] Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population (2008)
  • Author(s): Kawasaki A, Kyogoku C, Ohashi J, Miyashita R, Hikami K, Kusaoi M, Tokunaga K, Takasaki Y, Hashimoto H, Behrens TW, Tsuchiya N.
  • Journal Title: Support for a crucial role of intron 1 polymorphisms Arthritis Rheum 58 Pages: 826-834
  • Peer Reviewed
• [Journal Article] Differential association of HLA-DRB1 alleles in Japanese patients with early rheumatoid arthritis in relationship to autoantibodies to cyclic citrullinated peptide (2007)
  • Author(s): Furuya T, Hakoda M, Ichikawa N, Higami K, Nanke Y, Yago T, Kobashigawa T, Tokunaga K, Tsuchiya N, Kamatani N, Kotake S.
  • Journal Title: Clin Exp Rheumatol 25 Pages: 219-224
  • Peer Reviewed
• [Journal Article] Association of human CD22 gene polymorphism with susceptibility to limited cutaneous systemic sclerosis (2007)
  • Author(s): Hitomi Y, Tsuchiya N, Hasegawa M, Fujimoto M, Takehara K, Tokunaga K, Sato S.
  • Journal Title: Tissue Antigens 69 Pages: 242-249
  • Peer Reviewed
• [Journal Article] Role of APRIL (TNFSF13) polymorphisms in the susceptibility to systemic lupus erythematosus in Japanese (2007)
  • Author(s): Kawasaki A, Tsuchiya N, Ohashi J, Murakami Y, Fukazawa T, Kusaoi M, Matsuta K, Hashimoto H, Tokunaga K.
  • Journal Title: Rheumatology 46 Pages: 776-782
  • Peer Reviewed
• [Journal Article] A compass that points to lupus : Genetic studies on type I interferon pathway (2007)
  • Author(s): Kyogoku C, Tsuchiya N.
  • Journal Title: Genes Immun 8 Pages: 445-455
  • Peer Reviewed
• [Journal Article] Diversity of human immune system multigene families and its implication in the genetic background of rheumatic diseases (2007)
  • Author(s): Tsuchiya N, Kyogoku C, Miyashita R, Kuroki K.
  • Journal Title: Curr Med Chem 14 Pages: 421-439
  • Peer Reviewed
• [Presentation] 日本人における全身性エリテマトーデス感受性遺伝子 (2009)
  • Author(s): 土屋尚之
  • Organizer: 第37回日本臨床免疫学会
  • Place of Presentation: 東京
  • Year and Date: 20091113-20091115
• [Presentation] Association of SPI1 3-untranslated region polymorphism with systemic lupus erythematosus (2009)
  • Author(s): Hikami K, Kawasaki A, Ito I, Koga M, Ito S, Hayashi T, Goto D, Matsumoto I, Tsutsumi A, Takasaki Y, Hashimoto H, Arinami T, Sumida T, Tsuchiya N.
  • Organizer: The American Society of Human Genetics 59th Annual Meeting
  • Place of Presentation: Honolulu (USA)
  • Year and Date: 20091020-20091024
• [Presentation] Association of FAM167A (C8orf13)-BLK region with systemic sclerosis (2009)
  • Author(s): Ito I, Kawaguchi Y, Kawasaki A, Hasegawa M, Ohashi J, Kawamoto M, Fujimoto M, Takehara K, Sato S, Hara M, Tsuchiya N.
  • Organizer: 2009 American College of Rheumatology Annual Scientific Meeting
  • Place of Presentation: Philadelphia (USA)
  • Year and Date: 20091017-20091022
• [Presentation] リウマチ性疾患の遺伝的背景-共通性と異質性 (2009)
  • Author(s): 土屋尚之
  • Organizer: 第53回日本リウマチ学会総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-04-24
• [Presentation] 全身性エリテマトーデスの遺伝素因におけるI型インターフェロン関連遺伝子の役割 (2008)
  • Author(s): 土屋尚之, 川崎綾
  • Organizer: 第52回日本リウマチ学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20080420-20080423
• [Presentation] A single nucleotide polymorphism associated with expression of interferon regulatory factor 5 (IRF5) is a genetic risk factor for systemic sclerosis (2008)
  • Author(s): Ito I, Kawasaki A, Hikami K, Hasegawa M, Fujimoto M, Takehara K, Sato S, Tsuchiya N.
  • Organizer: 2008 American College of Rheumatology Annual Scientific Meeting
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2008-10-27
• [Presentation] Replication of the association between C8orf13-BLK region and systemic lupus erythematosus in a Japanese population (2008)
  • Author(s): Ito I, Kawasaki A, Hayashi T, Matsumoto I, Ito S, Tsutsumi A, Ohashi J, Hom G, Graham RR, Takasaki Y, Hashimoto H, Behrens TW, Sumida T, Tsuchiya N.
  • Organizer: 2008 American College of Rheumatology Annual Scientific Meeting
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2008-10-26
• [Presentation] Association of STAT4 polymorphisms with systemic lupus erythematosus in a Japanese population (2008)
  • Author(s): Kawasaki A, Ito I, Hikami K, Hayashi T, Matsumoto I, Ito S, Tsutsumi A, Koga M, Arinami T, Graham RR, Hom G, Ohashi J, Takasaki Y, Hashimoto H, Behrens TW, Sumida T, Tsuchiya N.
  • Organizer: 2008 American College of Rheumatology Annual Scientific Meeting
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2008-10-26
• [Presentation] 全身性エリテマトーデスの疾患感受性遺伝子解析 (2008)
  • Author(s): 土屋尚之
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] A SNP in IRF5 intron 1 defines a protective haplotype against SLE in Japanese (2007)
  • Author(s): Kawasaki A, Kyogoku C, Miyashita R, Ohashi J, Tokunaga K, Kusaoi M. Takasaki Y, Hashimoto H, Behrens TW, Tsuchiya N.
  • Organizer: 2007 American College of Rheumatology Annual scientific Meeting, Boston
  • Place of Presentation: Boston (USA)
  • Year and Date: 20071106-20071111
• [Presentation] Total number of risk alleles in four susceptibility genes as a marker for genetic risk to SLE (2007)
  • Author(s): Tsuchiya N, Kawasaki A, Takasaki Y, Hashimoto H, Ohashi J.
  • Organizer: 2007 American College of Rheumatology Annual scientific Meeting, Boston
  • Place of Presentation: Boston (USA)
  • Year and Date: 20071106-20071111
• [Remarks] ホームページ等
  • URL: http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/CCP004.html