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Development of the personalized medicine for pulmonary arterial hypertension by the pharmacogenomic approach

Research Project

Project/Area Number 26460213
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionKobe Pharmaceutical University

Principal Investigator

Emoto Noriaki  神戸薬科大学, 薬学部, 教授 (30294218)

Co-Investigator(Kenkyū-buntansha) 辻 剛  社会医療法人神鋼記念会(総合医学研究センター), 総合医学研究センター, 助手(移行) (00437493)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肺高血圧症 / 個別化医療 / ゲノム / エンドセリン受容体拮抗薬 / 遺伝子多型 / ボセンタン / 遺伝子多型・変異
Outline of Final Research Achievements

The purpose of this study was to create the clinical database for pulmonary hypertension and to identify genomic biomarkers that predict effectiveness and adverse effects of disease targeting drugs. An exploratory analysis of 1,936 SNPs in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using DMET chips, was performed. We extracted 16 SNPs using Jonckheere-Terpstra trend test, and by using multiplex logistic analysis, we identified two SNPs in two genes significantly associated with bosentan-induced liver injury. We conducted ROC analysis by using 2 SNPs and 2 items of non-genetic factor, and we constructed predictive model for bosentan-induced liver injury. These results may provide not only a way to personalized medicine for PAH but also novel mechanistic insights on drug-induced liver dysfunction.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Potsdam(ドイツ)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Association of Apical Longitudinal Rotation with Right Ventricular Performance in Patients with Pulmonary Hypertension: Insights into Overestimation of Tricuspid Annular Plane Systolic Excursion.2015

    • Author(s)
      Motoji Y, Tanaka H, Fukuda Y, Sano H, Ryo K, Sawa T, Miyoshi T, Imanishi J, Mochizuki Y, Tatsumi K, Matsumoto K, Emoto N, Hirata K.
    • Journal Title

      Echocardiography.

      Volume: 33 Issue: 2 Pages: 207-215

    • DOI

      10.1111/echo.13036

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stable Somatic Gene Expression in Mouse Lungs Following Electroporation-mediated Tol2 Transposon Delivery.2015

    • Author(s)
      Muliawan HS, Nakayama K, Yagi K, Ikeda K, Yagita K, Hirata K, Emoto N.
    • Journal Title

      Kobe J Med Sci.

      Volume: 61

    • NAID

      120005661466

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of Coils and a Pulmonary Vasodilator to Reduce Pulmonary Hypertension in a Patient with Interstitial Pneumonia and Scleroderma2015

    • Author(s)
      Teguh Ryanto GR, Nakayama K, Takaya T, Fujimoto D, Kinutani H, Shinkura Y, Mori S, Okada T, Nishii T, Kono A, Shinke T, Emoto N, Hirata K.
    • Journal Title

      Internal Medicine

      Volume: 54 Issue: 21 Pages: 2721-2726

    • DOI

      10.2169/internalmedicine.54.4976

    • NAID

      130005106611

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension.2015

    • Author(s)
      Satwiko MG, Ikeda K, Nakayama K, Yagi K, Hocher B, Hirata K, Emoto N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 465 Issue: 3 Pages: 356-362

    • DOI

      10.1016/j.bbrc.2015.08.002

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Right ventricular function and right-heart echocardiographic response to therapy predict long-term outcome in patients with pulmonary hypertension.2015

    • Author(s)
      Sano H, Tanaka H, Motoji Y, Fukuda Y, Sawa T, Mochizuki Y, Ryo K, Matsumoto K, Emoto N, Hirata K.
    • Journal Title

      Can J Cardiol.

      Volume: 31 Issue: 4 Pages: 529-536

    • DOI

      10.1016/j.cjca.2015.01.027

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current trends in the management of pulmonary hypertension associated with respiratory disease in institutions approved by the Japanese Respiratory Society.2014

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

      Respir Investig

      Volume: 52 Issue: 3 Pages: 167-172

    • DOI

      10.1016/j.resinv.2013.11.003

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.2014

    • Author(s)
      Makino K, Jinnin M, Aoi J, Kajihara I, Makino T, Fukushima S, Sakai K, Nakayama K, Emoto N, Yanagisawa M, Ihn H.
    • Journal Title

      PLoS One.

      Volume: 22 Issue: 5 Pages: e97972-e97972

    • DOI

      10.1371/journal.pone.0097972

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Utility of combining assessment of right ventricular function and right atrial remodeling as a prognostic factor for patients with pulmonary hypertension.2014

    • Author(s)
      Fukuda Y, Tanaka H, Motoji Y, Ryo K, Sawa T, Imanishi J, Miyoshi T, Mochizuki Y, Tatsumi K, Matsumoto K, Shinke T, Emoto N, Hirata K.
    • Journal Title

      Int J Cardiovasc Imaging.

      Volume: 30 Issue: 7 Pages: 1269-1277

    • DOI

      10.1007/s10554-014-0460-6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current state of endothelin receptor antagonism in hypertension and pulmonary hypertension.2014

    • Author(s)
      Miyagawa K, Emoto N.
    • Journal Title

      Ther Adv Cardiovasc Dis.

      Volume: 8 Issue: 5 Pages: 1269-1277

    • DOI

      10.1177/1753944714541511

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Balloon pulmonary angioplasty: an additional treatment option to improve the prognosis of patients with chronic thromboembolic pulmonary hypertension.2014

    • Author(s)
      Taniguchi Y, Miyagawa K, Nakayama K, Kinutani H, Shinke T, Okada K, Okita Y, Hirata KI, Emoto N.
    • Journal Title

      EuroIntervention.

      Volume: 10 Issue: 4 Pages: 518-525

    • DOI

      10.4244/eijv10i4a89

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 肺高血圧症の治療戦略:新薬をどう生かすか2017

    • Author(s)
      江本憲昭
    • Organizer
      第81回日本循環器学会総会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Pulmonary hypertension in Congenital Heart Diseases: Treat and Repair Approach.2016

    • Author(s)
      Noriaki Emoto
    • Organizer
      The 15th Vietnam National Congress of Cardiology
    • Place of Presentation
      ハノイ ヴェトナム
    • Year and Date
      2016-10-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 肺高血圧症Update:診断のピットフォールと病態を踏まえた治療法2016

    • Author(s)
      江本憲昭
    • Organizer
      第64回日本心臓病学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Burden of Congenital Heart Disease in Developed Country versus Developing Country2016

    • Author(s)
      Noriaki Emoto
    • Organizer
      Cardiology Update 2016
    • Place of Presentation
      ジョグジャカルタ インドネシア
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Step by step diagnosis and management of pulmonary hypertension, why are pulmonary hypertension patients frequently underdiagnosed?2016

    • Author(s)
      Noriaki Emoto
    • Organizer
      The 25th Annual scientific Meeting of the Indonesian Heart Association
    • Place of Presentation
      ジャカルタ インドネシア
    • Year and Date
      2016-04-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ET-1 in the Heart in Health and Disease2015

    • Author(s)
      Noriaki Emoto
    • Organizer
      14th International Conference on Endothelin: Pathophysiology and Therapeutics
    • Place of Presentation
      Savannah, USA
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Diagnosis and Treatment of Pulmonary Hypertension2017

    • Author(s)
      Emoto N.
    • Total Pages
      17
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Remarks] 江本研究室 業績

    • URL

      http://www.kobepharma-u.ac.jp/clinical/publications/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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