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Pharmacogenetic studies on the influence of ALDH2 gene polymorphisms on the vasodilation induced by organic nitrates

Research Project

Project/Area Number 20390160
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionKyushu University

Principal Investigator

SASAGURI Toshiyuki  Kyushu University, 大学院・医学研究院, 教授 (30261209)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Fumi  九州大学, 大学院・医学研究院, 助教 (50274436)
MATSUMURA Kiyoshi  九州大学, 病院, 助教 (70285469)
三輪 宜一  九州大学, 大学院・医学研究院, 助教 (60346773)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2009: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2008: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywords硝酸薬 / ニトログリセリン / 二硝酸イソソルビド / 狭心症 / 血管拡張 / 2型アルデヒド脱水素酵素 / 遺伝子多型 / ゲノム薬理学 / 薬理遺伝学 / 硝酸イソソルビド
Research Abstract

To examine whether polymorphisms at codon 487 of aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerin (GTN)-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is more effective in each genotype, we performed a crossover trial using sublingual spray of GTN and ISDN. Maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, the time required for dilation was longer in the ^*1/^*2 and ^*2/^*2 genotypes than ^*1/^*1. In contrast, ISDN-induced dilation did not differ among genotypes. The time required for GTN dilation was shorter than that for ISDN dilation among ^*1 allele carriers, whereas GTN and ISDN dilation did not differ among participants carrying ^*2/^*2. These results suggested that the response to GTN was significantly delayed in ^*2 allele carriers. GTN dilated the artery more quickly than ISDN in ^*1/^*1 and ^*1/^*2, but not in ^*2/^*2.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (47 results)

All 2011 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (23 results) Book (3 results) Remarks (3 results)

  • [Journal Article] Differential effects of organic nitrates on arterial diameter among healthy Japanese participants with different mitochondrial aldehyde dehydrogenase 2 genotypes : randomised crossover trial.2011

    • Author(s)
      Sakata S, Yoshihara T, Arima H, Shiraishi F, Oniki H, Takahashi-Yanaga F, Matsumura K, Sasaguri T.
    • Journal Title

      BMJ Open in press.

    • Related Report
      2010 Final Research Report
  • [Journal Article] β_1-adrenergic receptor gene polymorphisms and the acute response to atenolol in healthy young Japanese subjects.2011

    • Author(s)
      Sasaguri T, et al
    • Journal Title

      J Pharmacol Sci

      Volume: (in press)

    • NAID

      10029893413

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Celecoxib and 2,5-dimethyl-celecoxib prevent cardiac remodeling inhibiting Akt-mediated signal transduction in an inherited DCM mouse model.2011

    • Author(s)
      Fan X, et al.
    • Journal Title

      J Pharmacol Exp Ther

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of type 2 iodothyronine deiodinase in dilated cardiomyopathy.2010

    • Author(s)
      Wang Y-Y, et al
    • Journal Title

      Cardiovasc Res

      Volume: 87 Pages: 636-646

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biological actions of green tea catechins on cardiac troponin C.2010

    • Author(s)
      Tadano N, et al
    • Journal Title

      Br J Pharmacol.

      Volume: 161 Pages: 1034-1043

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sex differences in the risk profile and male predominance in silent brain infarction in community-dwelling elderly subjects : the Sefuri brain MRI study.2010

    • Author(s)
      Takashima Y, et al
    • Journal Title

      Hypertens Res

      Volume: 33 Pages: 748-752

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway.2010

    • Author(s)
      Yoshihara T, et al
    • Journal Title

      Mol Cancer

      Volume: 9 Pages: 245-245

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiproteinuric effect of cilnidipine in hypertensive Japanese treated with renin-angiotensin-system inhibitors-A multicenter, open, randomized trial using 24-hour urine collection.2010

    • Author(s)
      Miwa Y, et al
    • Journal Title

      Clin Exp Hypertens

      Volume: 32 Pages: 400-405

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knockout of the 1-pgds gene aggravates obesity and atherosclerosis in mice.2009

    • Author(s)
      Tanaka R, et al.
    • Journal Title

      Biochem Biophys Res Commun 378

      Pages: 851-856

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Propyl gallate, a strong antioxidant, increases the Ca^<2+> sensitivity of cardiac myofilament.2009

    • Author(s)
      Tadano N, et al.
    • Journal Title

      J Pharmacol Sci 109

      Pages: 456-458

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertension and white matter lesions are independently associated with apathetic behavior in healthy elderly subjects : the Sefuri brain MRI study.2009

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

      Hypertens Res 32

      Pages: 586-590

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic effect of beta-adrenoceptor blockers using a mouse model of dilated cardiomvovathy with a troponin mutation.2009

    • Author(s)
      Zhan DY, et al.
    • Journal Title

      Cardiovasc Res 84

      Pages: 64-71

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The involvement of aldosterone in cyclic stretch-mediated activation of NADPH oxidase in vascular smooth muscle cells.2009

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

      Hypertens Res 32

      Pages: 690-699

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knockout of the L-PGDS gene induces obesity and atherosclerosis in mice.2009

    • Author(s)
      Tanaka R., et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 378

      Pages: 861-856

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Propyl gallate, a strong antioxidant, increases the Ca^<2+> sensitivity of cardiac myofilament.2009

    • Author(s)
      Tadano N, et al.
    • Journal Title

      J. Pharmacol. Sci. 109

      Pages: 456-458

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYPIAI activation and cell cycle arrest in vascular endothelial cells.2008

    • Author(s)
      Han z., et al.
    • Journal Title

      Cardiovasc. Res. 77

      Pages: 809-818

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects.2008

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

      Hypertens. Res. 31

      Pages: 75-81

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of serum lipocalin-type prostaglandin D synthase levels with subclinical atherosclerosis in untreated asymptomatic subjects.2008

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

      Hypertens. Res. 31

      Pages: 1931-1939

    • NAID

      10024827726

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型ガニトログリセリンおとび二硝酸イソソルビドの血管拡張作用に印ぼす効果2010

    • Author(s)
      吉原達也, 坂田智子, 白石富美恵, 鬼木秀幸, 市島久仁彦, 大坪俊夫, 三輪宜一, 高橋富美, 有馬久富, 松村潔, 笹栗俊之
    • Organizer
      第31回日本臨床薬理学会年会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] ALDH2の遺伝子多型がニトログリセリンの薬効に印ぼす影響2010

    • Author(s)
      笹栗俊之, 坂田智子, 吉原達也, 白石富美恵, 松村潔
    • Organizer
      第20回日本循環薬理学会年会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型がニトログリセリンおよび二硝酸イソソルビドの血管拡張作用に及ぼす影響2010

    • Author(s)
      坂田智子, 松村潔, 三輪宜一, 鬼木秀幸, 市島久仁彦, 吉原達也, 高橋富美, 白石富美恵, 大坪俊夫, 笹栗俊之
    • Organizer
      第33回日本高血圧学会年会
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation] Effect of aldehyde dehydrogenase-2 gene polymorphism on vasodilatory response of brachial artery induced by nitroglycerin.2010

    • Author(s)
      Sakata S, Matsumura K, Miwa Y, Oniki H, Ichishima K, Arima H, Takahashi-Yanaga F, Yoshihara T, Shiraishi F, Iida M, Sasaguri T
    • Organizer
      23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      バンクーバー
    • Related Report
      2010 Final Research Report
  • [Presentation] Influence of aldehyde dehydrogenase-2 gene polymorphism on vasodilatation induced by organic nitrates in healthy human subjects.2010

    • Author(s)
      Sakata S, Ichijima K, Oniki H, Miwa Y, Arima H, Matsumura K, Yoshihara T, Takahashi-Yanaga F, Shiraishi F, Sasaguri T
    • Organizer
      WorldPharma 2010
    • Place of Presentation
      コペンハーゲン
    • Related Report
      2010 Final Research Report
  • [Presentation] Influence of aldehyde dehydrogenase-2 gene polymorphism on vasodilatation induced by organic nitrates in healthy human subjects.2010

    • Author(s)
      Sakata S, et al
    • Organizer
      World Pharma 2010
    • Place of Presentation
      Bella Center (Copenhagen, Denmark)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Effect of aldehyde dehydrogenase-2 gene polymorphism on vasodilatory response of brachial artery induced by nitroglycerin.2010

    • Author(s)
      Sakata S, et al
    • Organizer
      23rd Scientific Meeting of the International Society of Hypertension
    • Place of Presentation
      Vancouver Convention Center (Vancouver, Canada)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型がニトログリセリンおよび二硝酸イソソルビドの血管拡張作用に及ぼす影響2010

    • Author(s)
      坂田智子, 他
    • Organizer
      第33回 日本高血圧学会総会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] ALDH2の遺伝子多型がニトログリセリンの薬効に及ぼす影響2010

    • Author(s)
      笹栗俊之, 他
    • Organizer
      第20回 日本循環薬理学会
    • Place of Presentation
      札幌市教育文化会館(札幌市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型がニトログリセリンおよび二硝酸イソソルビドの血管拡張作用に及ぼす効果2010

    • Author(s)
      吉原達也, 他
    • Organizer
      第31回 日本臨床薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 拡張型心筋症モデルマウスにおけるcelecoxibの効果2010

    • Author(s)
      範雪麗, 他
    • Organizer
      第83回 日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] トロポニン変異による拡張型心筋症マウスモデルを用いたβ-アドレナリン受容体遮断薬の治療効果の検討2010

    • Author(s)
      戦冬雲, 他
    • Organizer
      第83回 日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] プロピルガレートのマウス心機能に対する影響2010

    • Author(s)
      杜成坤, 他
    • Organizer
      第83回 日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] トロポニン変異による拡張型心筋症モデルマウスの心臓表現型に対する遺伝的背景の影響2010

    • Author(s)
      李蕾, 他
    • Organizer
      第83回 日本薬理学会年会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] リポカリン型プロスタグランジンD合成酵素(L-PGDS)遺伝子欠損は高脂肪食負荷マウスにおいて肥満及び動脈硬化を促進する2009

    • Author(s)
      三輪宜一, 他
    • Organizer
      第32回 日本高血圧学会総会
    • Place of Presentation
      大津
    • Related Report
      2009 Annual Research Report
  • [Presentation] 夜勤業務と血圧上昇、メタボリック症候群の関連2009

    • Author(s)
      村谷博美, 他
    • Organizer
      第32回 日本高血圧学会総会
    • Place of Presentation
      大津
    • Related Report
      2009 Annual Research Report
  • [Presentation] Differentiation-inducing factor-1はVEGFR2の発現を低下させることによりin vitroおよびin vivoにおいて血管新生を阻害する2009

    • Author(s)
      吉原達也, 他
    • Organizer
      第68回 日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Differentiation-inducing factor-1はVEGFR2の発現を低下させることにより血管新生を阻害する2009

    • Author(s)
      吉原達也, 他
    • Organizer
      第30回 日本臨床薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] トロポニン変異による拡張型心筋症ノックインマウスモデルの生存とリモデリングに対するメトプロロールとカルペジロールの効果.2009

    • Author(s)
      戦冬雲, 他.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] 拡張型心筋症と心筋梗塞におけるDio2を介した局所的心臓ハイパーサイロイデイズム.2009

    • Author(s)
      王媛媛, 他.
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Association of serum lipocalin-type prostaglandin D synthase levels with subclinical atherosclerosis in untreated asymptomatic subjects.2009

    • Author(s)
      Miwa Y., et al.
    • Organizer
      第73回日本循環器学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2008 Annual Research Report
  • [Presentation] レニン-アンジオテンシン系阻害薬投与下でのシルニジピンの蛋白尿減少効果-24時間家庭蓄尿での検討-2008

    • Author(s)
      三輪宜一, 他.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] β_1アドレナリン受容体遺伝子多型のアテノロール感受陛への影響の検討.2008

    • Author(s)
      三輪宜一, 他.
    • Organizer
      第29回日本臨床薬理学会年会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Book] NEW薬理学(改訂第6版)(抗狭心症薬)2011

    • Author(s)
      笹栗俊之
    • Publisher
      南江堂
    • Related Report
      2010 Final Research Report
  • [Book] 抗狭心症薬(分担執筆部分):田中千賀子・加藤隆一編『NEW薬理学』(改訂第6版)2011

    • Author(s)
      笹栗俊之(分担執筆部分)
    • Total Pages
      662
    • Publisher
      南江堂
    • Related Report
      2010 Annual Research Report
  • [Book] 降圧薬のコンビネーションセラピー2009

    • Author(s)
      笹栗俊之
    • Total Pages
      170
    • Publisher
      時間薬理学的観点からみた降圧薬の使い方
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/clipharm/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/clipharm/index.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/clipharm/index.html

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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