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Studies on genetic testing for the possible diagnosis of aspirin resistance

基因检测可能诊断阿司匹林抵抗的研究

基本信息

批准号：
15390179
负责人：
MURATA Mitsuru
金额：
$ 8.32万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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.

最近的研究表明，对阿司匹林和其他抗血小板药物的耐药性是一种公认的状态。那些对阿司匹林治疗有抗药性的人更容易复发血栓形成。因此，研究发现阿司匹林抵抗的基因对预防动脉粥样硬化血栓形成事件是极其重要的，动脉粥样硬化血栓形成事件是这个国家的主要死亡原因。本研究的目的是分析阿司匹林抵抗与血栓形成和止血相关基因变异的关系，为血栓形成的个体化治疗提供基础数据。我们首先建立了最佳的实验条件，在体外评估阿司匹林抵抗，使用血小板功能分析仪，PFA 100。在大多数情况下，向正常富血小板血浆中加入高浓度阿司匹林延长了闭塞时间。然而，添加低浓度的阿司匹林也会这样做，但大约30%的正常个体对阿司匹林没有反应（即，在临界值范围内）。对阿司匹林"耐药"的人的特征是具有高基础血小板反应性，通过其他血小板功能测试评估的高血小板功能（在全血聚集仪WBA-Neo和使用富血小板血浆的传统光学聚集仪中的胶原蛋白刺激的血小板功能）。我们发现了几种可能与阿司匹林抵抗相关的遗传多态性。我们的研究结果提示处方前评估抗血小板治疗的疗效。前瞻性研究是必要的，以建立遗传多态性和抗血小板治疗的结果之间的关系和因果关系。

项目成果

期刊论文数量（42）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Relation Between Development of Nephropathy and the p22phox C242T and Receptor for Advanced Glycation End Product G1704T Gene Polymorphisms in Type 2 Diabetic Patients

2型糖尿病患者肾病发生与p22phox C242T及晚期糖基化终产物G1704T受体基因多态性的关系

DOI：
发表时间：
2004
期刊：
Diabetes Care 27・2
影响因子：
0
作者：
Matsunaga-Irie S;Maruyama T;Yamamoto Y;Motohashi Y;Hirose H;Murata M et al.
通讯作者：
Murata M et al.

Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation : randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype

通过补充叶酸预防动脉粥样硬化的评估：针对每种 MTHFR C677T 基因型的随机、双盲、安慰剂对照试验

DOI：
发表时间：
2005
期刊：
J Hum Genet 50
影响因子：
0
作者：
Miyaki K;Murata M et al.
通讯作者：
Murata M et al.

Genetic analysis and expression studies identified a novel mutation (W486C) as a molecular basis of congenital coagulation factor XII deficiency.

遗传分析和表达研究确定了一种新的突变（W486C）作为先天性凝血因子 XII 缺乏的分子基础。

DOI：
发表时间：
2004
期刊：
Blood Coagulation and Fibrinolysis 15
影响因子：
0
作者：
Ishii K;Oguchi S;Moriki T;Yatabe Y;Takeshita E;Murata M et al.
通讯作者：
Murata M et al.

Novel resistin polymorphisms : Association with serum resistin level in Japanese obese individuals.

新型抵抗素多态性：与日本肥胖个体血清抵抗素水平的关联。

DOI：
发表时间：
2004
期刊：
Horm Metab Res 36(8)
影响因子：
0
作者：
Azuma K;Oguchi S;Matsubara M;Mamizuka T;Murata M;Kikuchi H;Watanabe K;Katsukawa F;Yamazaki H;Shimada A;Saruta T.
通讯作者：
Saruta T.

Telomere length of normal leukocytes is affected by a functional polymorphism of hTERT