Identification of susceptibility gene for lumbar disc herniation and clarification of its molecular pathogenesis

• Project/Area Number: 19209049
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: IKEGAWA Shiro The Institute of Physical and Chemical Research, 骨関節疾患研究チーム, チームリーダー (30272496)
• Co-Investigator(Kenkyū-buntansha): FURUICHI Tatsuya 独立行政法人理化学研究所, 骨関節疾患 研究チーム, 上級研究員 (30392103) ; INABA Ikuyo 独立行政法人理化学研究所, 骨関節疾患 研究チーム, リサーチアソシエイト (60415081)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000); Fiscal Year 2008: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2007: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
• Keywords: 骨・関節疾患 / 椎間板ヘルニア / 椎間板変性症 / 疾患感受性遺伝子 / 相関解析 分子病態 / 脊椎脊髄病学 / 腰椎椎間板ヘルニア / 相関解析 / COLIIA1 / アスポリン / アジア

Research Abstract

椎間板ヘルニアの発症機構、病態の分子レベルでの解明の為にその原因遺伝子(疾患感受性遺伝子)を同定し、同定した遺伝子、疾患感受性多型の機能解析を行なった。以下の成果を得た。1) 新規の原因遺伝子THBS2とMMP9を同定した。THBS2の感受性アレルでは、異常なスプライシングが起こり、細胞外基質分解酵素であるMMPとの結合が低下することを証明した。2) アスポリンのD14多型が椎間板変性症と相関することを発見した。

Research Products

• [Journal Article] Association of the tag SNPs in the human SKT Gene (KIAA1217) with lumbar disc herniation (2009)
  • Author(s): Karasugi T, Semba K, Hirose Y, Kelempisioti A, Nakajima M, Miyake A, Furuichi T, Kawaguchi Y, Mikami Y, Chiba K, Kamata M, Ozaki K, Takahashi A, Makela P, Karppinen J, Kimura T, Kubo T, Toyama Y, Yamamura KI, Mannikko M, Mizuta H, Ikegawa S
  • Journal Title: J Bone Miner Res (Epub ahead of print) Pages: 0-0
  • Peer Reviewed
• [Journal Article] A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation (2008)
  • Author(s): Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S
  • Journal Title: Am J Hum Genet 82(5) Pages: 1122-9
  • Peer Reviewed
• [Journal Article] Association of the asporin D14 allele with lumbar-disc degeneration in Asians (2008)
  • Author(s): Song YQ, Cheung KM, Ho DW, Poon SC, Chiba K, Kawaguchi Y, Hirose Y, Alini M, Grad S, Yee AF, Leong JC, Luk KD, Yip SP, Karppinen J, Cheah KS, Sham P, Ikegawa S, Chan D
  • Journal Title: Am J Hum Genet 82(3) Pages: 744-7
  • Peer Reviewed
• [Journal Article] Functional polymotphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc disease (2008)
  • Author(s): Hirose Y, 他
  • Journal Title: Am J Hum Genet 82 Pages: 1122-1129
  • Peer Reviewed
• [Journal Article] Association of the Aspor in D14 allele with lumbar disc degeneration in Asians (2008)
  • Author(s): Song Y-Q, 他
  • Journal Title: Am J Hum Genet 82 Pages: 744-747
  • Peer Reviewed
• [Journal Article] Association of the Asporin D14 allele with lumbar disc degeneration in Asians. (2008)
  • Author(s): Song Y-Q, Cheung KMC, Ho DWH, Poon SCS, Chiba K, Kawaguchi Y, Hirose Y, Alini M, Grad S, Yee AFY, Leong J CY, Luk KDK, Yip S-P, Karppinen J, Cheah KSE, Sham P, Ikegawa S, Chan D.
  • Journal Title: Am J Hum Genet (in press)
  • Peer Reviewed
• [Journal Article] A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation (2007)
  • Author(s): Mio F, Chiba K, Hirose Y, Kawaguchi Y, Mikami Y, Oya T, Mori M, Kamata M, Matsumoto M, Ozaki K, Tanaka T, Takahashi A, Kubo T, Kimura T, Toyama Y, Ikegawa S
  • Journal Title: Am J Hum Genet 81(6) Pages: 1271-7
  • Peer Reviewed
• [Journal Article] A functional polymorphism in COL11A1,which encodes the alpha 1 chain of type XI collagen,is associated with susceptibility to lumbar dischemiation. (2007)
  • Author(s): Mio F, Chiba K, Hirose Y, Kawaguchi Y, Mikami Y, Oya T, Mori M, Kamata M, Matsumoto M, Ozaki K, Tanaka T, Takahashi A, Kubo T. Kimura T, Toyama Y, Ikegawa S.
  • Journal Title: Am J Hum Genet 81 Pages: 1271-1277
  • Peer Reviewed
• [Presentation] 腰椎椎間板ヘルニアの全ゲノム相関解析 (2008)
  • Author(s): 唐杉 樹ほか
  • Organizer: 第23回 日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-24
• [Presentation] From genome to bone and joint diseases (2008)
  • Author(s): 池川 志郎
  • Organizer: 第13回アジア太平洋リウマチ学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-08
• [Presentation] 腰椎椎間板ヘルニアの全ゲノム相関解析 (2008)
  • Author(s): 唐杉樹, ほか
  • Organizer: 第53回 日本人類遺伝学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-28
• [Presentation] Genetic analysis of bone and joint diseases; From human, from mouse (2008)
  • Author(s): 池川 志郎
  • Organizer: 5th Bone Biology Forum
  • Place of Presentation: 静岡
  • Year and Date: 2008-08-22
• [Presentation] From Human, from Mouse: Integrated approach of human and mouse genetics toward the gene for bone and joint diseases (2008)
  • Author(s): 池川 志郎
  • Organizer: The 17th International Rheumatology Symposium
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] 腰椎椎間板ヘルニアの全ゲノム相関解析 (2008)
  • Author(s): 唐杉 樹ほか
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 横浜
• [Presentation] From Genome to Disease, Gene to Medicine: Identification of susceptibility genes for common bone and joint diseases and clarification of molecular pathogenesis (2007)
  • Author(s): 池川 志郎
  • Organizer: THE INDIAN SOCIETY OF DEVELOPMENTAL BIOLOGISTS (ISDB)
  • Place of Presentation: Agra,India
  • Year and Date: 2007-10-18
• [Presentation] From Genome to Disease,Gene to Medicine:Identification of susceptibility genes for common bone and joint diseases and clarification of molecular pathogenesis. (2007)
  • Author(s): Ikegawa S.
  • Organizer: The Indian Society of Developmental Biologists(ISDB)
  • Place of Presentation: Conference Room,Hotel Holiday Inn,Agra India.
  • Year and Date: 2007-10-18
• [Presentation] 骨・関節疾患のゲノム解析.疾患感受性遺伝子の同定から医療へ (2007)
  • Author(s): 池川 志郎
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-14
• [Presentation] Unraveling the genetic basis of common bone and joint diseases (2007)
  • Author(s): 池川 志郎
  • Organizer: The 8th Regional Osteoporosis Conference
  • Place of Presentation: HongKong
  • Year and Date: 2007-05-20
• [Remarks] ホームページ
  • URL: http://www.riken.go.jp/lab-www/OA-team/index.html
• [Remarks]
  • URL: http://www.riken.jp/lab-www/OA-team/index.html
• [Remarks]
  • URL: http://www.riken.jp/lab-www/OA-team/index.html
• [Patent(Industrial Property Rights)] 椎間板変性関連疾患感受性遺伝子およびその用途(トロンボスポンディン2遺伝子、マトリックスメタロプロテアーゼ2遺伝子、及びマトリックスメタロプロテアーゼ9遺伝子による椎間板変性症、及び椎間板ヘルニアの疾患感受性の診断と治療) (2008)
  • Inventor(s): 池川志郎
  • Industrial Property Rights Holder: 理化学研究所
  • Filing Date: 2008-09-30
• [Patent(Industrial Property Rights)] 椎間板変性関連疾患感受性遺伝子およびその用途 (2008)
  • Inventor(s): 池川志郎
  • Industrial Property Rights Holder: 理化学研究所
  • Filing Date: 2008-09-30
  • Overseas
• [Patent(Industrial Property Rights)] 椎間板変性関連疾患感受性遺伝子およびその用途(トロンボスポンディン2遺伝子、マトリックスメタロプロテアーゼ2遺伝子、及びマトリックスメタロプロテアーゼ9遺伝子による椎間板変性症、及び椎間板ヘルニアの疾患感受性の診断と治療) (2007)
  • Inventor(s): 池川 志郎
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 2007-257345
  • Filing Date: 2007-10-01