Molecular mechanism of statin intolerance in Japanese: Toward precision strategy in atherosclerotic cardiovascular disease.
| Project/Area Number |
18K08051
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(6 results)
Research Products
(29 results)
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[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.).
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Journal Title
N Engl J Med
Volume: 387
Issue: 20
Pages: 1855-1864
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 27
Issue: 4
Pages: 375-396
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2020-04-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Drug Metab Pharmacokinet.
Volume: 34
Issue: 6
Pages: 387-396
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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[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.
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Journal Title
Circulation Journal
Volume: 82
Issue: 4
Pages: 1008-1016
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Int'l Joint Research
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