| 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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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | thrombosis / antithrombotic therapy / antiplatelet therapy / platelet function / genetic polymorphism / tailor-made medicine / 遣伝子多型 |
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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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