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高血圧感受性遺伝子群の同定

Research Project

Project/Area Number 20018020
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionEhime University

Principal Investigator

三木 哲郎  Ehime University, プロテオ医学研究センター, 教授 (00174003)

Co-Investigator(Kenkyū-buntansha) 小原 克彦  愛媛大学, 大学院・医学系研究科, 准教授 (30260384)
田原 康玄  愛媛大学, 大学院・医学系研究科, 講師 (00268749)
名倉 潤  愛媛大学, 大学院・医学系研究科, 講師 (70304607)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2009: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2008: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywords高血圧 / 遺伝子多型 / スクリーニング / 高血圧感受性遺伝子 / 血圧 / 大規模集団サンプル / ゲノム疫学
Research Abstract

主に候補遺伝子アプローチから、高血圧に感受性を示す遺伝子の探索・同定を行った。300種の候補遺伝子をスクリーニングしたところ、高血圧と強く関連する遺伝子Aを同定した。遺伝子Aと高血圧との関連は、年齢、性、BMIを調整後オッズ比で1.30(1.13-1.48)であり、アレルあたり収縮期血圧で1.5mmHg、拡張期血圧で0.75mmHgの上昇と相関した。この遺伝子について、英国を中心とする疾患感受性遺伝子解析コンソーシアム(Grobal BPgen)と共同で、Caucasianにおける高血圧感受性を検討した。その結果、高血圧に対する調整済みオッズ比は1.13(1.05-1.21)、p=5.9*10-4であり、Caucasianにおいても当該SNPは高血圧と関連することが明らかとなった。我が国では、ミレニアム・プロジェクトにおいて世界に先駆けてGWASに取り組み、その成果をベースとした本研究において高血圧感受性遺伝子を同定した。しかし、最近の遺伝子解析技術の進歩は当時の技術を遙かに凌駕しており、より網羅的な遺伝子解析からは更なる感受性遺伝子が同定されることが強く期待される。今後、より網羅的かつ大規模な遺伝子解析を進めることで高血圧をはじめとする多因子疾患の遺伝的背景を明らかにし、予防/臨床医学的にはハイリスク者の同定や疾患の層別化、医科学研究的には病態理解の深化と治療・創薬ターゲットの導出を進めていくことが必要であろう。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2010 2009 2008

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (6 results)

  • [Journal Article] A at single nucleotide polymorphism-358 is required for G at-420 to confer the highest plasma resistin in the general Japanese population.2010

    • Author(s)
      Onuma H, et al.
    • Journal Title

      PLoS One. 5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of the functional variant in the 3-hydroxy-3-methylglutaryl-coenzyme a reductase gene with low-density lipoprotein-cholesterol in Japanese2010

    • Author(s)
      Hiura Y, et al.
    • Journal Title

      Circ J 74

      Pages: 518-522

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vasopressin V1a receptor polymorphism and interval walking training effects in middle-aged and older people.2010

    • Author(s)
      Masuki S, et al.
    • Journal Title

      Hypertension 55

      Pages: 747-754

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is rs34861192 or rs1862513 a more promising variant for determining plasma resistin in an aged Japanese population?2010

    • Author(s)
      Osawa H, et al.
    • Journal Title

      Diabetologia 53

      Pages: 795-797

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of common polymorphisms is associated with development of hypertension : a 12-year follow-up from the Ohasama study.2010

    • Author(s)
      Watanabe Y, et al.
    • Journal Title

      Hypertens Res 33

      Pages: 129-34

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A pilot study suggests that the G/G genotype of resistin single nucleotide polymorphism at-420 may be an independent predictor of a reduction in fasting plasma glucose and insulin resistance by pioglitazone in type 2 diabetes.2009

    • Author(s)
      Makino H, et al.
    • Journal Title

      Endocr J 56

      Pages: 1049-1058

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of FTO genotype in the development of obesity in Japanese : the J-SHIPP study.2009

    • Author(s)
      Tabara Y, et al.
    • Journal Title

      Int J Obes 33

      Pages: 1243-1248

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of SLC6A9 gene variants with human essential hypertension.2009

    • Author(s)
      Ueno T, et al.
    • Journal Title

      J Atheroscler Thromb. 16

      Pages: 201-206

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PPARgamma Pro12Ala Pro/Pro and resistin SNP-420 G/G genotypes are synergistically associated with plasma resistin in the Japanese general population.2009

    • Author(s)
      Osawa H, et al.
    • Journal Title

      Clin Endocrinol 71

      Pages: 341-345

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-density association study and nomination of susceptibility genes forhyper tension in the Japanese National Project2008

    • Author(s)
      Kato N, Miki T, et.al.
    • Journal Title

      Human Molecular Genetics 17

      Pages: 617-627

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of hypertension-susceptibility genes and pathways by a systemic multiple candidate gene approach : the millennium genome project for hypertension2008

    • Author(s)
      Kohara K, Mild T, et.al.
    • Journal Title

      Hypertension Research 31

      Pages: 203-212

    • NAID

      10024359591

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistin, glomerular filtration rate, and insulin resistance2008

    • Author(s)
      Tabara Y, Miki T, et.al.
    • Journal Title

      Hypertension 51

      Pages: 708-714

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No association of INSIG2 gene rs7566605 polymorphism with being overwe ight in Japanese population2008

    • Author(s)
      Tabara Y, Mild T, et.al.
    • Journal Title

      Obesity 16

      Pages: 211-215

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood pressure is the main reterminant of the reflection wave in patientsw ith type 2 diabetes2008

    • Author(s)
      Tomita H, Miki T, et.al.
    • Journal Title

      Hypertension Research 31

      Pages: 493-500

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An association between decreased estimated glomerular filtration rate and arterial stiffness2008

    • Author(s)
      Kawamoto R, Mild T, et.al.
    • Journal Title

      Intern Med 47

      Pages: 593-598

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced high-molecular-weight adiponectin and elevated high-sensitivity C-reactive protein are synergistic risk factors for metabolic syndrome in a large-scale middle-aged to elderly population2008

    • Author(s)
      Tabara Y, Mild T, et.al.
    • Journal Title

      Hypertension 93

      Pages: 715-722

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An association between metabolic syndrome and the estimated glomerular filtration rate2008

    • Author(s)
      Kawamoto R, Miki T, et.al.
    • Journal Title

      Intern Med 47

      Pages: 1399-1406

    • NAID

      130000078949

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between serum gamma-glutamyl transferase level and prehype rtension among community-dwelling men2008

    • Author(s)
      Kawamoto R, Miki T, et.al.
    • Journal Title

      Tohoku J Exp Med 216

      Pages: 213-221

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 糖尿病感受性遺伝子の日本人における交差妥当性の検証と長期縦断ゲノム疫学研究による新規糖尿病発症との相関解析2009

    • Author(s)
      田原康玄, 他
    • Organizer
      弟52回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 一般住民において、PPARg Pro12Ala PrQ/Pro型とレジスチンSNP-420 G/G型は血中レジスチンと相乗的に関連する2009

    • Author(s)
      大澤春彦, 他
    • Organizer
      弟52回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] FTO遺伝子多型と肥満との相関に対する長期縦断的検討2009

    • Author(s)
      田原康玄, 他
    • Organizer
      第16回 日本遺伝子診療学会大会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] 左室肥大とBNP濃度との相関に対するNPPB遺伝子多型の交絡2009

    • Author(s)
      田原康玄, 他
    • Organizer
      第16回 日本遺伝子診療学会大会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] Interaction of NPPB genotype on the relationship between left ventricular hypertrophy and plasma BNP levels2009

    • Author(s)
      Tabara Y, et al.
    • Organizer
      The American Society of Human Genetics, 59th Annual Meeting.
    • Place of Presentation
      Hawaii, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規発症脳卒中患者に見られるCMB2008

    • Author(s)
      伊賀瀬、三木他
    • Organizer
      日本内科学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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