Development of the personalized prevention system for ischemic stroke by a genome-wide association study

• Project/Area Number: 18209023
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Mie University
• Principal Investigator: YAMADA Yoshiji Mie University, 生命科学研究支援センター, 教授 (90333286)
• Co-Investigator(Kenkyū-buntansha): ICHIHARA Sahoko 三重大学, 生命科学研究支援センター, 助教 (20378326) ; 小島 俊男 独立行政法人理化学研究所, ゲノム科学総合研究センター, チームリーダー (00311340)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Toshio 独立行政法人理化学研究所, 基盤研究所, チームリーダ
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥49,010,000 (Direct Cost: ¥37,700,000、Indirect Cost: ¥11,310,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000); Fiscal Year 2006: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
• Keywords: ゲノム / 関連解析 / オーダーメイド予防 / 脳血管障害 / アテローム血栓性脳梗塞 / 脳血栓 / 脳出血 / くも膜下出血

Research Abstract

候補遺伝子アプローチによる300遺伝子多型の関連解析を行い、IL6遺伝子-572G→C、ABCA1遺伝子-14C→T、IRAK1遺伝子A→C、C→T(Ser532Leu)、ROS1遺伝子G→C(Cys2229Ser)が脳血栓の発症に、IL6遺伝子-572G→C、LIMK1遺伝子-428G→Aが脳出血の発症に、UCP3遺伝子-55C→T、TNF遺伝子-863C→A、KIAA0319L遺伝子G→A(Gly243Asp)、CYP3A4遺伝子13989A→G(Ile118Val)がくも膜下出血の発症にそれぞれ関連することを見出した。次に、3つの独立した集団で合計6341例(脳血栓992例および対照5349例)についてゲノム全領域関連解析を行い、脳血栓発症と強く関連するCELSR1遺伝子と2個のSNPs、A→G(Thr2268Ala, rs6007897)およびA→G(Ile2107Val, rs4044210)を同定した。

Research Products

• [Journal Article] Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals (2008)
  • Author(s): Yoshiji Yamada, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Kimihiko Kato, Takeshi Hibino, Kiyoshi Yokoi, Sachiro Watanabe, Sahoko Ichihara, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa
  • Journal Title: Stroke 39 Pages: 2211-2218
  • Peer Reviewed
• [Journal Article] Genetic risk for myocardial infarction determined by polymorphisms of candidate genes in Japanese individuals (2008)
  • Author(s): Yoshiji Yamada, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Kiyoshi Yokoi, Hitoshi Matsuo, Sachiro Watanabe, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Sahoko Ichihara, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa
  • Journal Title: J Med Genet 45 Pages: 216-221
  • Peer Reviewed
• [Journal Article] Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals (2008)
  • Author(s): Yamada Y, Metoki N, Yoshida H, Satoh K, Kato K, Hibino T, Yokoi K, Watanabe S, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y
  • Journal Title: Stroke 39 Pages: 2211-2218
  • Peer Reviewed
• [Journal Article] Association of genetic variants with atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome (2008)
  • Author(s): Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y
  • Journal Title: Int J Mol Med 21 Pages: 801-808
  • Peer Reviewed
• [Journal Article] Proinflammatory gene polymorphisms and ischemic stroke (2008)
  • Author(s): Yamada Y, Ichihara S, Nishida T
  • Journal Title: Curr Pharm Des 14 Pages: 3590-3600
  • Peer Reviewed
• [Journal Article] Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians (2007)
  • Author(s): Noriyuki Fuku, Kyong Soo Park, Yoshiji Yamada, Yutaka Nishigaki, Young Min Cho, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Kimihiko Kato, Kiyoshi Yokoi, Yoshinori Nozawa, Hong Kyu Lee, Masashi Tanaka
  • Journal Title: Am J Hum Genet 80 Pages: 407-415
  • Peer Reviewed
• [Journal Article] Mitochondrial haplogroup A is a genetic risk factor for atherothromboticcerebral infarction inJapanesefemales (2007)
  • Author(s): Yutaka Nishigaki, Yoshiji Yamada, Noriyuki Fuku, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Kimihiko Kato, Kiyoshi Yokoi, Sachiyo Yamaguchi, Yoshinori Nozawa, Masashi Tanaka
  • Journal Title: Mitochondrion 7 Pages: 72-79
  • Peer Reviewed
• [Journal Article] 生活習慣病のゲノム疫学(1):生活習慣病のオーダーメイド予防システムの開発 (2007)
  • Author(s): 山田 芳司
  • Journal Title: 現代医学 55 Pages: 153-157
• [Journal Article] 脳血管障害のオーダーメイド予防聖 (2007)
  • Author(s): 山田 芳司
  • Journal Title: 脳神経外科速報 17 Pages: 1320-1329
• [Journal Article] 脳血管障害のゲノム疫学とオーダーメイド予防 (2007)
  • Author(s): 山田 芳司
  • Journal Title: 脳卒中 29 Pages: 715-720
  • NAID: 130004542919
• [Journal Article] Mitochondrial haplogroup A is a genetic risk factor for atherothrombotic cerebral infarction in Japanese females (2007)
  • Author(s): Nishigaki Y, Yamada Y, Fuku N, Matsuo H, Segawa T, Watanabe S, Kato K, Yokoi K, Yamaguchi S, Nozawa Y, Tanaka M
  • Journal Title: Mitochondrion (In press)
• [Journal Article] Genetic risk for ischemic and hemorrhagic stroke (2006)
  • Author(s): Yoshiji Yamada, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Sahoko Ichihara, Kimihiko Kato, Takashi Kameyama, Kiyoshi Yokoi, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Yoshinori Nozawa
  • Journal Title: Arterioscler Thromb Vasc Biol 26 Pages: 1920-1925
  • Peer Reviewed
• [Journal Article] Genetic risk for ischemic and hemorrhagic stroke (2006)
  • Author(s): Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, Kato K, Kameyama T, Yokoi K, Matsuo H, Segawa T, Watanabe S, Nozawa Y
  • Journal Title: Arterioscler Thromb Vasc Biol 26 Pages: 1920-1925
• [Journal Article] Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis (2006)
  • Author(s): Yamaguchi S, Yamada Y, Metoki N, Yoshida H, Satoh K, Ichihara S, Kato K, Kameyama T, Yokoi K, Matsuo H, Segawa T, Watanabe S, Nozawa Y
  • Journal Title: Int J Mol Med 18 Pages: 871-883
• [Journal Article] Identification of genetic factors and development of genetic risk diagnosis systems for cardiovascular diseases and stroke (2006)
  • Author(s): Yamada Y
  • Journal Title: Circ J 70 Pages: 1240-1248
  • NAID: 110004809958
• [Journal Article] 心筋梗塞・脳血管障害のオーダーメイド予防システムの開発 (2006)
  • Author(s): 山田芳司
  • Journal Title: 心臓 38 Pages: 1175-1180
  • NAID: 120001859821
• [Journal Article] 循環器疾患の遺伝要因の解明と遺伝子リスク診断システムの開発 (2006)
  • Author(s): 山田芳司
  • Journal Title: 心臓 38 Pages: 1159-1159
  • NAID: 120001859820
• [Journal Article] Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study
  • Author(s): Yoshiji Yamada, Noriyuki Fuku, Masashi Tanaka, Yukitoshi Aoyagi, Motoji Sawabe, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Kimihiko Kato, Sachiro Watanabe, Yoshinori Nozawa, Aki Hasegawa, Toshio Kojima
  • Journal Title: Atherosclerosis (in press)
  • Peer Reviewed
• [Journal Article] Association of a polymorphism of BCHE with ischemic stroke in Japanese individuals with chronic kidney disease
  • Author(s): Oguri M, Kato K, Yokoi K, Yoshida T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Tanaka M, Nozawa Y, Yamada Y
  • Journal Title: Mol Med Rep (In press)
  • Peer Reviewed
• [Journal Article] Identification of CELSRl as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study
  • Author(s): Yamada Y, Fuku N, Tanaka M, Aoyagi Y, Sawabe M, Metoki N, Yoshida H, Satoh K, Kato K, Watanabe S, Nozawa Y, Hasegawa A, Kojima T
  • Journal Title: Atherosclerosis (In press)
  • Peer Reviewed
• [Journal Article] Genetic factors for ischemic and hemorrhagic stroke in Japaneseindividuals
  • Author(s): Yoshiji Yamada, NorifUmi Metoki, Hidemi Yoshida, Kei Satoh, Kimihiko Kato, Takeshi Hibino, Kiyoshi Yokoi, Sachiro Watanabe, Sahoko Ichihara, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa
  • Journal Title: Stroke (In press)
  • Peer Reviewed
• [Journal Article] Association of candidate gene polymorphisms with atherothrombotic cerebral infarction among Japanese indivuduals with metabolic syndrome
  • Author(s): Yoshiji Yamada, Kimihiko Kato, Mitsutoshi Oguri, Tetsuro Yoshida, Kiyoshi Yokoi, Sachiro Watanabe, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Sahoko Ichihara, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa
  • Journal Title: Int J Mol Med (In press)
  • Peer Reviewed
• [Journal Article] 生活習慣病のゲノム疫学(2):脳血管障害のオーダーメイド予防
  • Author(s): 山田 芳司
  • Journal Title: 現代医学 (印刷中)
  • NAID: 40015886665
• [Presentation] Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals (2009)
  • Author(s): Takanori Nagahiro, Mitsutoshi Oguri, Mizuho Hirmatsu, Hiroshi Matsuo, Yumiko Yamamura, Yoshiyuki Kataoka, Manabu Miura, Yoshihisa Shibata, Yoshihiro Hanaki, Haruo Kamiya, Miyoshi Ohno, Kimihiko Kato, Tetsuo Fujimaki, Kazuhiro Yajima, Kiyoshi Yokoi, Sachiro Watanabe, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Associations of genetic variants with ischemic stroke in Japanese individuals with metabolic syndrome (2009)
  • Author(s): Yoshiyuki Kataoka, Mitsutoshi Oguri, Mizuho Hiramatsu, Hiroshi Matsuo, Takanori Nagahiro, Yumiko Yamamura, Manabu Miura, Yoshihisa Shibata, Yoshihiro Hanaki, Haruo Kamiya, Miyoshi Ohno, Kimihiko Kato, Tetsuo Fujimaki, Kazuhiro Yajima, Kiyoshi Yokoi, Sachiro Watanabe, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals (2008)
  • Author(s): Mitsutoshi Oguri, Haruo Kamiya, Miyoshi Ohno, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Kimihiko Kato, Kiyoshi Yokoi, Sachiro Watanabe, Yukitoshi Aoyagi, Masashi Tanaka, Yoshinori Nozawa, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: The 81th Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-11
• [Presentation] Identification of the genetic risk for myocardial infarction and ischemic stroke by candidate gene approach and genome-wide association study (2008)
  • Author(s): Yoshiji Yamada
  • Organizer: The 11th Cardiovascular Genomics and Atherosclerosis Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-10-31
• [Presentation] Identification of genetic risk and development of personalized preventionsystems for cardiovascular diseases (2008)
  • Author(s): 山田 芳司
  • Organizer: 第72回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-29
• [Presentation] Prediction of genetic risk for metabolic syndrome and atherosclerotic disease (2007)
  • Author(s): Yoshiji Yamada
  • Organizer: The 4th International Joint Symposiumof Korea Biomedial Genomic Research Associationand Center for Genomic Science
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2007-12-07
• [Presentation] Genetic risk for metabolic syndrome and atherosclerotic diseases (2007)
  • Author(s): Yoshiji Yamada
  • Organizer: 10th Cardiovascular Genomics and AtherosclerosisSymposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2007-04-13
• [Presentation] 脳血管障害関連遺伝子の探索:候補遺伝子解析 (2007)
  • Author(s): 山田 芳司
  • Organizer: 第32回日本脳卒中学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2007-03-22
• [Presentation] Prediction of genetic risk for myocardial infarction and stroke (2007)
  • Author(s): Yoshiji Yamada
  • Organizer: 12th World Congress on Advances in Oncology and 10th International Symposium on Molecular Medicine
  • Place of Presentation: Crete, Greece
• [Presentation] Women with mitochondrial haplogroup A are susceptible to atherothrombotic cerebral infarction (2007)
  • Author(s): Yutaka Nishigaki, Yoshiji Yamada, Noriyuki Fuku, Masashi Tanaka
  • Organizer: The 59th American Academy of Neurology Annual Meeting
  • Place of Presentation: Boston, USA
• [Presentation] Genetic risk for ischemic and hemorrhagic stroke (2007)
  • Author(s): Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Kimihiko Kato, Takashi Kameyama, Kiyoshi Yokoi, Sahoko Ichihara, Yoshiji Yamada
  • Organizer: 第71回日本循環器学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Prediction of the genetic risk for myocardial infarction and stroke (2006)
  • Author(s): Yoshiji Yamada
  • Organizer: 5th Congress of Asian Pacific Society of Atherosclerosis and Vascular Diseases
  • Place of Presentation: Jeju, Korea
• [Presentation] Identification of Genetic Factors and Development of Genetic Risk Diagnosis Systems for Cardiovascular Diseases (2006)
  • Author(s): Yoshiji Yamada
  • Organizer: 第70回記念日本循環器学会総会・学術集会「日本心臓財団佐藤賞」受賞講演
  • Place of Presentation: 名古屋
• [Book] Genomics and Clinical Medicine(Dhavendra Kumar, David Weatherall, eds.)(Human functional genomics and proteomics) (2008)
  • Author(s): Yoshiji Yamada, Sahoko Ichihara, Masaharu Takemura
  • Publisher: New York : Oxford University Press(in press)
• [Book] Genomics and Clinical Medicine(Dhavendra Kumar, David Weatherall, eds.)(Osteoporosis and related phenotypes) (2008)
  • Author(s): Yoshiji Yamada
  • Publisher: New York : Oxford University Press
• [Book] ゲノム多型による脳血管障害の発症予測 : バイオ解析・診断技術のテーラーメイド医療への応用 (2006)
  • Author(s): 山田芳司
  • Total Pages: 250
  • Publisher: シーエムシー出版
• [Book] Clinical Cardiovascular Genetics : Principle and Practice(Dhavendra Kumar, Perry Elliot, eds.)(Genetics of Stroke)
  • Author(s): Yoshiji Yamada, Sahoko Ichihara, Tamotsu Nishida
  • Publisher: New York : Oxford University Press(in press)
• [Book] Clinical Cardiovascular Genetics : Principle and Practice(Dhavendra Kumar, Perry Elliot, eds.)(Genetics of coronary heart disease)
  • Author(s): Yoshiji Yamada, Sahoko Ichihara, Tamotsu Nishida
  • Publisher: New York : Oxford University Press(in press)
• [Book] Clinical Cardiovascular Genetics : Principle and Practice
  • Author(s): Yamada Y, Ichihara S, Nishida T
  • Publisher: Oxford University Press(in press)
• [Book] Clinical Cardiovascular Genetics:Principle and Practice
  • Author(s): Yoshiji Yamada, Sahoko Ichihara, Tamotsu Nishida
  • Publisher: Oxford University Press(In press)
• [Remarks] クオルセイバー有限責任事業組合(QOLSaviour Limited Liability Partnership)設立、リサーチディレクター(兼任)就任(平成17年10月)
  • URL: http://www.gandgscience.co.jp/QOL/index.html
• [Remarks]
  • URL: http://www.genomarker.jp/
• [Remarks] 三重大学疾患ゲノム研究センター設立(平成20年9月)
  • URL: http://www.mie-u.ac.jp/research/
• [Remarks] 生命科学研究支援センターヒト機能ゲノミクス部門ホームページ
  • URL: http://www.lsrc.mie-u.ac.jp/human/
• [Remarks]
  • URL: http://www.mie-u.ac.jp/research/
• [Remarks]
  • URL: http://www.lsrc.mie-u.ac.jp/human/
• [Patent(Industrial Property Rights)] 脳梗塞の遺伝的リスク検出法 (2009)
  • Inventor(s): 山田芳司, 小島俊男, 村上和美
  • Industrial Property Rights Holder: 三重大学, 理化学研究所
  • Industrial Property Number: 2009-011495
  • Filing Date: 2009-01-22
• [Patent(Industrial Property Rights)] アテローム血栓性脳梗塞に関する遺伝子検出方法 (2006)
  • Inventor(s): 田中雅嗣, 山田芳司, 野澤義則, 岡田英樹
  • Industrial Property Rights Holder: 田中雅嗣, 山田芳司, 財団法人岐阜県国際バイオ研究所, G＆Gサイエンス株式会社
  • Industrial Property Number: 2006-165295
  • Filing Date: 2006-06-14
• [Patent(Industrial Property Rights)] 脳血管障害の遺伝的リスク検出法 (2006)
  • Inventor(s): 山田芳司, 野澤義則, 岡田英樹
  • Industrial Property Rights Holder: 山田芳司, G＆Gサイエンス株式会社, 財団法人岐阜県国際バイオ研究所
  • Industrial Property Number: 2006-244526
  • Filing Date: 2006-09-08
• [Patent(Industrial Property Rights)] 脳梗塞の遺伝的リスク検出法
  • Inventor(s): 山田芳司、小島俊男、村上和美
  • Industrial Property Rights Holder: 三重大学、理化学研究所
  • Industrial Property Number: 2009-011495
• [Patent(Industrial Property Rights)] 心筋梗塞の遺伝的リスク検出法
  • Inventor(s): 山田芳司、野澤義則、武安岳史
  • Industrial Property Rights Holder: 山田芳司、G&Gサイエンス株式会社、財団法人岐阜県国際バイオ研究所
  • Industrial Property Number: 2006-288908
• [Patent(Industrial Property Rights)] 脳血管障害の遺伝的リスク検出法
  • Inventor(s): 山田芳司、野澤義則、岡田英樹
  • Industrial Property Rights Holder: 山田芳司、G&Gサイエンス株式会社、財団法人岐阜県国際バイオ研究所
  • Industrial Property Number: 2006-244526
• [Patent(Industrial Property Rights)] 心筋梗塞のリスク診断方法
  • Inventor(s): 山田芳司、横田充弘
  • Industrial Property Rights Holder: 財団法人名古屋産業科学研究所、財団法人岐阜県国際バイオ研究所
• [Patent(Industrial Property Rights)] 高血圧のリスク診断方法
  • Inventor(s): 山田芳司、横田充弘
  • Industrial Property Rights Holder: 財団法人名古屋産業科学研究所、財団法人岐阜県国際バイオ研究所
• [Patent(Industrial Property Rights)] 冠動脈攣縮のリスク診断方法
  • Inventor(s): 山田芳司、横田充弘
  • Industrial Property Rights Holder: 財団法人名古屋産業科学研究所、財団法人岐阜県国際バイオ研究所
• [Patent(Industrial Property Rights)] 冠動脈形成術後再狭窄のリスク診断方法
  • Inventor(s): 山田芳司、横田充弘
  • Industrial Property Rights Holder: 財団法人名古屋産業科学研究所、財団法人岐阜県国際バイオ研究所