2005 Fiscal Year Final Research Report Summary
Studies on genetic testing for the possible diagnosis of aspirin resistance
| Project/Area Number |
15390179
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Keio University |
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Principal Investigator |
MURATA Mitsuru Keio University, School of Medicine, Professor, 医学部, 教授 (50174305)
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| Project Period (FY) |
2003 – 2005
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| Keywords | thrombosis / antithrombotic therapy / antiplatelet therapy / platelet function / genetic polymorphism / tailor-made medicine |
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| Research Abstract |
Recent studies have revealed that resistance to aspirin and other antiplatelet drugs is a commonly recognized status. Those on aspirin therapy who are resistant to this drug are more prone to the recurrence of thrombosis. Thus, research to find genes responsible for aspirin resistance is extremely important to prevent atherothrombotic events, which are the leading cause of death in this country. The purpose of this study was to analyze the mechanisms of aspirin resistance in relationship with the variability in genes responsible for thrombosis and hemostasis, and to obtain basic data for individualized treatment of thrombosis. We first established the optimal experimental conditions for the in vitro assessment of aspirin resistance, using a platelet function analyzer, PFA100. Addition of aspirin at high concentration to normal platelet-rich plasma prolonged the occlusion time over the cut-off range in most cases. Addition of low concentration of aspirin, however, also did so but 〜30% of normal individuals failed to respond to aspirin (i.e., remained within the cut-off range). Those who are "resistant" to aspirin were characteristic as having high basal platelet reactivity, high platelet function as assessed by other platelet function tests (collagen-stimulated platelet function in a whole-blood aggregometer WBA-Neo and conventional optical aggregometer using platelet rich plasma). We found several genetic polymorphisms that are possibly associated with aspirin resistance. Our results are suggestive for the pre-prescription assessment of the efficacies of antiplatelet therapies. Prospective studies are necessary to establish the relationship and causation between genetic polymorphisms and the outcome of antiplatelet therapies.
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Research Products
(44 results)
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[Journal Article] ProteinS□K196E mutation as a genetic risk factor for deep vein thrombosis.2006
Author(s)
Kimura R, Honda S, Kawasaki T, Tsuji H, Madoiwa S, Sakata Y, Kojima T, Murata M, Nishigami K, Chiku M, Hayashi T, Kokudo Y, Okayama A, Tomoike H, Ikeda Y, Miyata T.
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Journal Title
BLOOD 107(4)
Pages: 1737-1738
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel resistin polymorphisms : Association with serum resistin level in Japanese obese individuals.2004
Author(s)
Azuma K, Oguchi S, Matsubara M, Mamizuka T, Murata M, Kikuchi H, Watanabe K, Katsukawa F, Yamazaki H, Shimada A, Saruta T.
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Journal Title
Horm Metab Res 36(8)
Pages: 564-570
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura.2004
Author(s)
Uchida T, Wada H, Mizutani M, Iwashita M, Ishihara H, Shibano T, Suzuki M, Matsubara Y, Soejima K, Matsumoto M, Fujimura Y, Ikeda Y, Murata M.
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Journal Title
Blood 104(7)
Pages: 2081-2083
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bernard-Soulier syndrome with a homozygous 13-bp deletion in the signal peptide-coding region of platelet glycoprotein Ibss gene.2003
Author(s)
Watanabe R, Ishibashi T, Saitoh Y, Shichishima T, Maruyama Y, Enomoto Y, Handa M, Oda A, Ambo H, Murata M, Ikeda Y.
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Journal Title
Blood Coagulation and Fibrinolysis 14(4)
Pages: 387-394
Description
「研究成果報告書概要(欧文)」より
