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

Molecular mechanism of statin intolerance in Japanese: Toward precision strategy in atherosclerotic cardiovascular disease.

Research Project

Project/Area Number 18K08051
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKanazawa Medical University

Principal Investigator

KAJINAMI Kouji  金沢医科大学, 医学部, 教授 (40262563)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsスタチン / 動脈硬化性心血管疾患 / 薬剤不耐 / 個別化医療 / 筋障害 / 遺伝子多型 / 副作用報告 / レセプトデータ / 薬物不耐
Outline of Final Research Achievements

In order to investigate potential mechanism of statin intolerance in Japanese, we enrolled 91 patients with statin intolerance and 150 true control subjects with longer than 2-yr statin treatment. By means of genome-wide association study technique, we identified modest association (p=5.72E-6) between chromosome 6 and clinical event of statin-associated myopathy. However, no mechanistic proposal could be identified between this locus and myopathy even though our extensive literature review.

Academic Significance and Societal Importance of the Research Achievements

スタチンによるコレステロール低下療法は動脈硬化性心血管疾患予防に不可欠であるが、そのアドヒアランス低下(不耐)は疾患予防を妨げる。そこでスタチン不耐の原因解明と対策確立を目的に、不耐の中心理由である筋障害に関与する遺伝素因について、2年以上の長期服用により忍容性が確認された「真の対照例」を設定し、全ゲノムワイド連鎖解析により探索した。その結果第6染色体に弱いシグナルが同定された。また筋障害重症度と連鎖の強さに関連は認めなかった。今後の症例集積によって詳細な解析が可能になることから、日本人に特徴的な治療方針策定につながると期待される。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 2018

All Journal Article (19 results) (of which Int'l Joint Research: 13 results,  Peer Reviewed: 18 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Book (1 results)

  • [Journal Article] Thrombotic Risk Stratification and Intensive Statin Therapy for Secondary Prevention of Coronary Artery Disease ― Insights From the REAL-CAD Study ―2022

    • Author(s)
      Natsuaki M, Morimoto T, Iimuro S, Nagai R, Kimura T, the REAL-CAD Investigators (Kajinami K, et al), et al..
    • Journal Title

      Circulation Journal

      Volume: 86 Issue: 9 Pages: 1416-1427

    • DOI

      10.1253/circj.CJ-22-0315

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2022-08-25
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease2022

    • Author(s)
      O’Donoghue ML, Rosenson RS, Gencer B, Lopez JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Ran X, Murphy SA, Wang H, Wu Y, Kassahun H, Sabatine MS, the OCEAN(a)-DOSE Trial Investigators (Kajinami K, et al.).
    • Journal Title

      N Engl J Med

      Volume: 387 Issue: 20 Pages: 1855-1864

    • DOI

      10.1056/nejmoa2211023

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A case of myopericarditis after the second dose of mRNA COVID-19 vaccine in a patient with a history of myopericarditis2022

    • Author(s)
      Fujibayashi K, Kajinami K
    • Journal Title

      Clin Med Insights Case Rep

      Volume: 15 Pages: 95476221138648-95476221138648

    • DOI

      10.1177/11795476221138648

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naive patients with acute ST elevation myocardial infarction2022

    • Author(s)
      Sawaguchi J, Saeki Y, Oda M, Takamura TA, Fujibayashi K, Wakasa M, Akao H, Kitayama M, Kawai Y, Kajinami K.
    • Journal Title

      Atherosclerosis Plus

      Volume: 50 Pages: 50-56

    • DOI

      10.1016/j.athplu.2022.09.002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity2022

    • Author(s)
      Oda M, Fujibayashi K, Wakasa M, Takano S, Fujita W, Kitayama M, Nakanishi H, Saito K, Kawai Y, Kajinami K
    • Journal Title

      Scand Cardiovasc J

      Volume: 56 Issue: 1 Pages: 180-186

    • DOI

      10.1080/14017431.2022.2085884

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glyceraldehyde-derived advanced glycation end-products are associated with the severity of cardiac function and heart failure in patients with diabetic cardiomyopathy2022

    • Author(s)
      Yasuda Y, Aoki H, Wakasa M, Fujita W, Kawai Y, Kajinami K
    • Journal Title

      Scand Cardiovasc J

      Volume: 56 Issue: 1 Pages: 208-216

    • DOI

      10.1080/14017431.2022.2095013

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Response to pre-dilatation with plain old balloons can predict target lesion revascularization after drug coated balloon angioplasty for de novo small coronary artery lesions.2022

    • Author(s)
      Takamura T, Kawai Y, Akita S, Oda M, Akao H, Nakagawa T, Takama S, Tsuchiya T, Kitayama M, Kajinami K.
    • Journal Title

      J Int Med Res

      Volume: 50 Issue: 8 Pages: 0605221113779-0605221113779

    • DOI

      10.1177/03000605221113779

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure2021

    • Author(s)
      Teerlink JR, Diaz R, Felker GM, McMurray JJV, GALACTIC-HF Investigators (Kajinami K, et al), et al.
    • Journal Title

      New England Journal of Medicine

      Volume: 384 Issue: 2 Pages: 105-116

    • DOI

      10.1056/nejmoa2025797

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] スタチン不耐の疫学と対策2021

    • Author(s)
      梶波康二
    • Journal Title

      Current Therapy

      Volume: 39 Pages: 837-843

    • Related Report
      2021 Research-status Report
  • [Journal Article] Guidelines on the Clinical Evaluation of Medicinal Products for Treatment of Dyslipidemia2020

    • Author(s)
      Yamashita Shizuya、Kouji Kajinami, et al.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 11 Pages: 1246-1254

    • DOI

      10.5551/jat.CR004

    • NAID

      130007933950

    • ISSN
      1340-3478, 1880-3873
    • URL

      https://pure.teikyo.jp/en/publications/02e4e9dc-386d-44e8-93dd-22ca589512fb

    • Year and Date
      2020-11-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial2020

    • Author(s)
      Koba S, Inoue I, Cyrille M, Lu C, Inomata H, Shimauchi J, Kajinami K.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 5 Pages: 471-484

    • DOI

      10.5551/jat.50963

    • NAID

      130007839059

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2020-05-01
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Statin Intolerance Clinical Guide 20182020

    • Author(s)
      Kajinami K, Tsukamoto K, Koba S, Inoue I, Yamakawa M, Suzuki S, Hamano T, Saito H, Saito Y, Masuda S, Nakayama T, Okamura T, Yamashita S, Kagawa T, Kaneyama J, Kuriyama A, Tanaka R, Hirata A: Statin Intolerance Clinical Guide Working Group
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 4 Pages: 375-396

    • DOI

      10.5551/jat.50948

    • NAID

      130007824993

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2020-04-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monitoring the roles of prothrombin activation fragment 1 and 2 (F1?+?2) in patients with atrial fibrillation receiving rivaroxaban and apixaban2020

    • Author(s)
      Ueno Ei-ichi、Fujibayashi Kosuke、Sawaguchi Jun、Yasuda Yushi、Takano Shintaro、Fujioka Nakaba、Kawai Yasuyuki、Fujita Harumi、Tanaka Yoshi、Kajinami Kouji
    • Journal Title

      Journal of Thrombosis and Thrombolysis

      Volume: 50 Issue: 2 Pages: 371-379

    • DOI

      10.1007/s11239-020-02079-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of cardiac resynchronization therapy in a patient with coronary sinus ostial atresia and persistent left superior vena cava2020

    • Author(s)
      Fujibayashi Kosuke、Saeki Yasuhiko、Sawaguchi Jun、Yasuda Yuushi、Ueno Eiichi、Takano Shintaro、Fujioka Nakaba、Kawai Yasuyuki、Kajinami Kouji
    • Journal Title

      Journal of Cardiology Cases

      Volume: 21 Issue: 3 Pages: 101-103

    • DOI

      10.1016/j.jccase.2019.11.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design2020

    • Author(s)
      Tada Hayato、Kajinami Kouji、et al.
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 9 Pages: e038623-e038623

    • DOI

      10.1136/bmjopen-2020-038623

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Real-World Data to Identify Hypercholesterolemia Patients on Suboptimal Statin Therapy2019

    • Author(s)
      Kajinami K, Ozaki A, Tajima Y, Yamashita S, Arai H, Teramoto T.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 26 Issue: 5 Pages: 408-431

    • DOI

      10.5551/jat.46201

    • NAID

      130007641196

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2019-05-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microdosing clinical study to clarify pharmacokinetic and pharmacogenetic characteristics of atorvastatin in Japanese hypercholesterolemic patients.2019

    • Author(s)
      Lee N, Maeda K, Fukizawa S, Ieiri I, Tomaru A, Akao H, Takeda K, Iwadare M, Niwa O, Masauji T, Yamane N, Kajinami K, Kusuhara H, Sugiyama Y.
    • Journal Title

      Drug Metab Pharmacokinet.

      Volume: 34 Issue: 6 Pages: 387-396

    • DOI

      10.1016/j.dmpk.2019.08.004

    • NAID

      50014558529

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment Patterns, Statin Intolerance, and Subsequent Cardiovascular Events Among Japanese Patients With High Cardiovascular Risk Initiating Statin Therapy2018

    • Author(s)
      Nagar S, Rane P, Fox K, Meyers J, Davis K, Beaubrun A, Inomata H, Qian Y, Kajinami K.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 4 Pages: 1008-1016

    • DOI

      10.1253/circj.CJ-17-0811

    • NAID

      130006528547

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Towards Effective Cost-Effectiveness Analysis in Atherosclerotic Cardiovascular Disease Prevention2018

    • Author(s)
      Kajinami K.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 4 Pages: 954-955

    • DOI

      10.1253/circj.CJ-18-0193

    • NAID

      130006528556

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] The circulating furin-cleaved/mature PCSK9 ratio as a novel prognostic marker in statin-naive patients with acute ST elevation myocardial infarction.2022

    • Author(s)
      Sawaguchi J, Saeki Y, Oda M, Takamura TA, Fujibayashi K, Wakasa M, Akao H, Kitayama M, Kawai Y, Kajinami K.
    • Organizer
      The 86th annual scientific meeting of the Japanese Circulation Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新たな残余リスクとしてのスタチン不耐.2022

    • Author(s)
      梶波康二
    • Organizer
      the 54th Annual Scientific Meeting of the Japan Atherosclerosis Society
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ABCC6遺伝子に片親性イドダイソミーによるナンセンス変異ホモ接合を認めた弾性線維性仮性黄色腫症の1例2021

    • Author(s)
      秋田恵理、小田美奈子、高村敬明、若狭 稔、赤尾浩慶、河合康幸、梶波康二
    • Organizer
      第53回日本動脈硬化学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Patient-centered, a multidisciplinary team-based approach in ASCVD prevention: new direction2021

    • Author(s)
      Kouji Kajinami
    • Organizer
      The 18th International Symposium on Atherosclerosis
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] スタチン不耐に関する診療指針:その理念と今後2020

    • Author(s)
      梶波康二
    • Organizer
      日本薬剤師会 令和元年度薬事情報センター実務担当者等研修会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] スタチン不耐への対応:指針2018の理念と課題2019

    • Author(s)
      梶波康二
    • Organizer
      第19回動脈硬化教育フォーラム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] スタチン不耐:指針2018と今後2019

    • Author(s)
      梶波康二
    • Organizer
      第51回日本動脈硬化学会総会・学術集会 学会企画3
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] スタチン不耐:新たな残余リスクとしての意義と対応2018

    • Author(s)
      梶波康二
    • Organizer
      第50回日本動脈硬化学会総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] スタチン不耐症例への対応2018

    • Author(s)
      梶波康二
    • Organizer
      第66回日本心臓病学会学術集会 シンポジウム10
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 循環器疾患最新の治療2022-2023(伊藤 浩、山下武志編) 脂質異常症(高脂血症)2022

    • Author(s)
      澤口 潤、梶波康二
    • Total Pages
      520
    • Publisher
      南江堂
    • ISBN
      9784524229956
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi