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全ゲノム罹患同胞対連鎖解析及び候補遺伝子関連解析による心筋梗塞感受性遺伝子の同定

Research Project

Project/Area Number 18018020
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionAichi Gakuin University

Principal Investigator

横田 充弘  Aichi Gakuin University, 歯学部, 教授 (50201851)

Co-Investigator(Kenkyū-buntansha) 井澤 英夫  名古屋大学, 大学院・医学系研究科, 講師 (80402569)
小畑 孝二  愛知学院大学, 歯学部, 助教 (40378229)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2007: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2006: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywords心筋梗塞 / 罹患同胞対 / マイクロサテライトマーカー / 連鎖解析 / 染色体連鎖解析 / 高密度SNPタイピング / 2番染色体連鎖領域 / 染色体連鎖領域
Research Abstract

「研究の目的」
本研究の目的は、心筋梗塞(MI)・冠動脈疾患(CAD)罹患同胞対を対象としたゲノムワイド罹患同胞対連鎖解析により、MI責任遺伝子座を同定し、その領域内に存在する遺伝子(多型)について大規模症例-対照関連解析を実施し、MI感受性遺伝子を同定することである。
「全ゲノム罹患同胞対連鎖解析」
MI・CAD罹患同胞対(227対、457例)を対象として、405個のマイクロサテライトマーカーを用いたゲノムワイド連鎖解析(GWLS)を実施し、5染色体6領域に候補連鎖領域を得た。1領域以外の5領域は、国内外の他の論文で未だ報告されていない。さらに、この内の3領域(LOD>2.2)に20マーカーを追加、設定し、連鎖領域の確認と狭小化を実施した。なお、この解析で得られたmax.peak LOD score=2.9である。
2番染色体候補連鎖領域に約3,000SNPsを設定し、高密度SNPタイピングをMI症例、対照各約500例で実施し、有力なMI候補遺伝子Aを発見した。現在、約4,000例以上の大規模関連解析を実施している。他の候補連鎖領域に関しても、同様に、大規模関連解析を実施する計画である。
「今後の課題」
現在、ゲノムワイド関連解析(GWAS)の研究支援を申請中である。受理されれば、GWLSとGWASが同時に可能となり、1)SNPを用いた連鎖解析の実施と、マイクロサテライトを用いた連鎖解析との比較、2)遺伝的素因の強い罹患同胞対症例と孤発例との感受性遺伝子の相同性、3)連鎖領域に位置する遺伝子の同時並行相関解析の実施、など、遺伝学的にも興味深い多面的な解析が可能になると考える。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006

All Journal Article (17 results) (of which Peer Reviewed: 5 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice.2007

    • Author(s)
      Xian wu Cheng
    • Journal Title

      Circulation Research 100

      Pages: 904-913

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of endogenous Mstl prevents apoptosis and cardiac dysfunction without affecting cardiac hypertrophy after myocardial infarction.2007

    • Author(s)
      Mari Odashima
    • Journal Title

      Circulation Research 100

      Pages: 1344-1352

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the relationship between sample size and risk factors for complex diseases based on a simulation study2007

    • Author(s)
      Yasuyuki Tomita
    • Journal Title

      Chem-Bio Informatics Journal 7(1)

      Pages: 1-11

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: A preliminary study2007

    • Author(s)
      Akiko Noda
    • Journal Title

      Chest 131

      Pages: 1694-1701

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adolescent obesity adversely affects blood pressure and resting heart rate.2007

    • Author(s)
      Reiao Baba
    • Journal Title

      Circulation Journal 71

      Pages: 722-726

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 循環器分野における個別化医療への展開-心筋梗塞感受性遺伝子の探索-2007

    • Author(s)
      宮田聖子
    • Journal Title

      最新医学 9月増刊号

      Pages: 281-291

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice.2007

    • Author(s)
      Xian Wu Cheng
    • Journal Title

      Circulation Research (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure.2006

    • Author(s)
      Sahoko Ichihara
    • Journal Title

      Cardiovascular Research 69

      Pages: 726-735

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Localization of cysteine protease, Cathepsin S, to the surface of vascular smooth muscle cells by association with Integrin αvβ 3.2006

    • Author(s)
      Xian Wu Cheng
    • Journal Title

      American Journal of Pathology 168

      Pages: 685-964

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prognostic value of pacing-induced mechanical alternans in patients with mild to moderate idiopathic dilated cardiomyopathy in sinus rhythm.2006

    • Author(s)
      Akihiro Hirashiki
    • Journal Title

      Journal of the American College of Cardiology 47

      Pages: 1382-1389

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats.2006

    • Author(s)
      Kohzo Nagata
    • Journal Title

      Hypertension 47

      Pages: 656-654

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure2006

    • Author(s)
      Xian Wu Chena
    • Journal Title

      Hypertension 48

      Pages: 979-987

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatine : Potential role of the RhoA - extracellular signal-regulated kinase serum response factor signalling pathway.2006

    • Author(s)
      Masako Saka
    • Journal Title

      Clinical and Experimental Pharmacology and Physiology 33

      Pages: 1164-1171

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Classification method for predicting the development of myocardial infarction by using the interaction between genetic and environmental factors.2006

    • Author(s)
      Yasuyuki Tomita
    • Journal Title

      Transactions on Bioinformatics (IPSJ Digital Courier) 47(2)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors.2006

    • Author(s)
      Sahoko Ichiara
    • Journal Title

      Journal of Molecular and Cellular Cardiology 41

      Pages: 318-329

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure.2006

    • Author(s)
      Masako Saka
    • Journal Title

      Journal of Cardiovascular Pharmacology 47

      Pages: 770-779

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuation of oxidative stress and cardiac dysfunction by, bisoprolol in an animal model of dilated cardiomyopathy.2006

    • Author(s)
      Sahoko Ichihara
    • Journal Title

      Biochemical and Biophysical Research Communications 350

      Pages: 105-113

    • Related Report
      2006 Annual Research Report
  • [Presentation] New concepts in translational cardiac research:Comprehensive approaches for identification of susceptibility genes to myocardial infarction.2007

    • Author(s)
      Mitsuhiro Yokota
    • Organizer
      13th World Congress on Heart Disease
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2007-07-29
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 動脈硬化性疾患のリスク検査法及びリスク検査用キット2007

    • Inventor(s)
      横田充弘
    • Industrial Property Rights Holder
      横田充弘
    • Industrial Property Number
      2007-305320
    • Filing Date
      2007-11-27
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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