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1.发明授权Method of diagnosing an increased risk of thrombus associated disease by detecting a certain t-PA polymorphism 失效通过检测某种t-PA多态性来诊断血栓相关疾病风险增加的方法
公开(公告)号：US5994080A
公开(公告)日：1999-11-30
申请号：US29023
申请日：1998-02-20
CPC分类号： C12Q1/6883 , C12Q2600/156
摘要： Blood clot formation is the key event in myocardial infarction. Besides increased coagulation, failure in blood clot lysis can induce undesired coronary thrombosis. Plasmin is essential for degradation of fibrin clots. Tissue-type plasminogen activator (t-PA) is the serine protease that converts plasminogen into plasmin. The association of the Alu insertion/deletion polymorphism in intron h of the t-pA gene to the risk of myocardial infarction was evaluated. Subjects with a documented history of myocardial infarction (n=162) and controls (n=258) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects of 55 years or older. Allele frequencies were 0.54 for the insertion allele (t-PA Alu-h I) and 0.46 for the deletion allele, and were in Hardy Weinberg equilibrium. Among subjects that were homozygous for the insertion (n=138) were more than twice as many subjects with myocardial infarction compared to those homozygous (n=75) for the deletion (relative risk of 2.04, (95% CI 1.03-4.03), adjusted for age, gender, smoking, total cholesterol, HDL cholesterol, systolic and diastolic blood pressure and body mass index). Our results provide strong evidence for an association of a particular allele, t-PA Alu-h I, of the t-PA gene with the occurrence of myocardial infarction.
摘要翻译： PCT No.PCT / EP96 / 03652。 371日期：1998年2月20日 102（e）1998年2月20日PCT PCT 1996年8月19日PCT公布。 出版物WO97 / 07240 日期1997年2月27日血液凝块形成是心肌梗死的关键事件。 除了凝血增加外，血块溶解失败也可能引起不良的冠状动脉血栓形成。 纤溶酶是纤维蛋白凝块降解所必需的。 组织型纤溶酶原激活剂（t-PA）是将纤溶酶原转化成纤溶酶的丝氨酸蛋白酶。 评估了t-pA基因内含子h中Alu插入/缺失多态性与心肌梗塞风险的关联。 从鹿特丹研究中抽取具有记录的心肌梗死史（n = 162）和对照组（n = 258）的受试者，这项研究是针对553岁或以上的7983例受试者的基于人群的队列研究。 插入等位基因（t-PA Alu-h I）的等位基因频率分别为0.54和缺失等位基因的等位基因频率分别为0.46和Hardy Weinberg平衡。 与纯合子（n = 75）相比，在插入（n = 138）中纯合子的受试者中，心肌梗死受试者的数目是两倍以上（相对危险度为2.04，（95％CI 1.03-4.03））， 调整年龄，性别，吸烟，总胆固醇，HDL胆固醇，收缩压和舒张压和体重指数）。 我们的结果为t-PA基因的特定等位基因t-PA Alu-h I与心肌梗塞发生的关联提供了有力的证据。
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