• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

代謝関連核内受容体遺伝子変異機能解析と肥満および脂質代謝異常

Research Project

Project/Area Number 17790603
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Metabolomics
Research InstitutionKanazawa University

Principal Investigator

野原 淳  金沢大学, 医学系研究科, 助手 (50313648)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords核内受容体 / 家族性複合型高脂血症 / 遺伝子多型 / リポ蛋白リパーゼ / 冠動脈硬化症 / 肥満 / メタボリックシンドローム / 遺伝子変異 / 脂肪肝 / コレステロール代謝
Research Abstract

核内受容体は特有のリガンド存在下に多数の遺伝子群を協調的に発現制御する転写因子で,フィブラート剤チアゾリジン剤は,それぞれ核内受容体PPARαおよびγを標的としている.PPARsに限らずRetinoid-X-receptor (RXR)とヘテロダイマーを形成して作用する核内受容体は,近年代謝に重要な多数の遺伝子の制御が示され,MetSに代表される代謝疾患治療戦略の重要な標的となっている.しかし,動物実験では明らかでもヒトでも同じとは限らない.この点で機能的遺伝子変異の同定は重要な知見を与えるものであり,また核内受容体を標的とする治療の開発には必須の情報でもある.
我々は高脂血症患者を対象としてPPARα,γ,δ,LXRα,Farnesoid-X-receptor (FXR),RXRγ遺伝子を検索,これまでに4個のミスセンス型(PPARαG395E, PPARαD140N, PPARγ2 P12A, RXRγG14S)と5'端非翻訳領域の多型1個(FXR -1g->t)を同定した.
RXRγ S14多型保持者は一般人(5%)と比較しFCHLに有意に高頻度(15%)で,TG高値およびHDL-C低値であり,冠動脈造影施行105例でcoronary stenosis indexが有意に高値であった.機能解析でRXRγS14は機能亢進型であり,リポ蛋白リパーゼプロモーター配列の転写をより強く抑制した.これらの結果よりRXRγ遺伝子はFCHLの遺伝子背景に何らかの寄与をしていると考えられた.
FXR遺伝子-1g->t多型では-1t保持者は有意にBMI高値,TC低値,拡張期血圧低値,腹部USで脂肪肝は低頻度と多彩な影響がみられた.またスタチンを投与した症例の解析では,FXR-1t保持者は-1gg保持者に比べより強くTchが低下,治療効果の予測にも重要と考えられた.

Report

(2 results)
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (12 results)

All 2007 2006 2005

All Journal Article (12 results)

  • [Journal Article] High frequency of a retinoid X receptor gamma gene variant in familial combined hyperlipidemia that associates with atherogenic dyslipidemia.2007

    • Author(s)
      Atsushi Nohara
    • Journal Title

      Arterioscler Thromb Vasc Biol 27(4)

      Pages: 923-928

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serum lipoprotein lipase mass : clinical significance of its measurement.2007

    • Author(s)
      Junji Kobayashi
    • Journal Title

      Clin Chim Acta 378(1-2)

      Pages: 7-12

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The relationship of percent body fat by bioelectrical impedance analysis with blood pressure, and glucose and lipid parameters.2006

    • Author(s)
      Junji Kobayashi
    • Journal Title

      J Atheroscler Thromb 13(5)

      Pages: 221-226

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The distribution of fasting and non-fasting serum triglyceride levels in Japanese population2006

    • Author(s)
      Junji Kobayashi
    • Journal Title

      Clin Chim Acta 374(1-2)

      Pages: 173-175

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CETP (cholesteryl ester transfer protein) promoter -1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia.2006

    • Author(s)
      Mutsuko Takata
    • Journal Title

      Clin Sci 111(5)

      Pages: 325-331

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of fenofibrate therapy on plasma ubiquinol-10 and ubiquinone-10 levels in Japanese patients with hyperlipidemia and type 2 diabetes mellitus.2006

    • Author(s)
      Akimichi Asano
    • Journal Title

      Pharmacotherapy. 26(4)

      Pages: 447-451

    • Related Report
      2006 Annual Research Report
  • [Journal Article] RXRg Gene Variant is Associate with Lower HDL, Lower Lipoprotein Lipase, Advanced Coronary Artery Disease, and More Frequent in Familial Combined Hyperlipidemia2005

    • Author(s)
      Nohara A
    • Journal Title

      Circulation (Supplement) 112(17)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ATP-binding cassette transporter G8 M429V polymorphism as a novel genetic marker of higher cholesterol absorption in hypercholesterolaemic Japanese subjects.2005

    • Author(s)
      Miwa K
    • Journal Title

      Clin Sci 109(2)

      Pages: 183-188

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term course of lipoprotein lipase (LPL) deficiency due to homozygous LPL(Arita) in a patient with recurrent pancreatitis, retained glucose tolerance, and atherosclerosis2005

    • Author(s)
      Kawashiri M
    • Journal Title

      J Clin Endocrinol Metab 90(12)

      Pages: 6541-6544

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of coronary artery ectasia with plasma insulin levels in Japanese men of heterozygous familial hypercholesterolemia with the low-density lipoprotein receptor gene mutation K790X.2005

    • Author(s)
      Murase Y
    • Journal Title

      Clin Chim Acta 355(1-2)

      Pages: 33-39

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Relationship of lipoprotein lipase and hepatic triacylglycerol lipase activity to serum adiponectin levels in Japanese hyperlipidemic men.2005

    • Author(s)
      Kobayashi J
    • Journal Title

      Horm Metab Res. 37(8)

      Pages: 505-509

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients.2005

    • Author(s)
      Mabuchi H
    • Journal Title

      J Atheroscler Thromb 12(2)

      Pages: 111-119

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi