Development of Japanese specific risk stratification and therapeutic strategy for ischemic heart disease by genetic information

本研究的具体目的是确定遗传因素，以了解导致日本人缺血性心脏病的分子机制，并根据订制药物制定风险分层和治疗策略。具体而言，本研究的研究对象为冠状动脉粥样硬化性缺血性心脏病和日本特异性冠状动脉血管痉挛性心脏病，确定了这两种疾病的患者，并从其血液中提取了基因组dna。利用这些基因组dna进行遗传分析，以确定导致冠状动脉粥样硬化、冠状动脉介入治疗后再狭窄和冠状动脉血管痉挛发病的日本特定遗传因素。通过利用这些信息，本研究的最终目的是为日本缺血性心脏病订制药物奠定基础。迄今为止，171名冠状动脉粥样硬化性缺血性心脏病患者（包括1名接受冠状动脉介入治疗的患者）和352名冠状动脉血管痉挛性缺血性心脏病患者被确定。收集这些受试者的临床资料和基因组dna。由于冠状血管痉挛研究的受试者作为冠状动脉粥样硬化分析的对照组，因此本研究的所有受试者均检测到17个基因多态性。在这17个基因中，包括已报道的与日本人心肌梗死相关的淋巴毒素基因和其他相关基因，以及我们之前发现与冠状血管痉挛相关的Rho激酶基因和对氧磷酶1基因。迄今为止，尚未研究感兴趣的表型、冠状动脉粥样硬化、冠状动脉介入治疗后再狭窄和冠状血管痉挛与候选基因之间的显著关联。然而，研究对象数量相对较少，候选基因数量有限。因此，为了达到本研究的目的，今后有必要增加研究对象并进行全基因组扫描。少

Specific aim of this study was to identify genetic factors for understanding the molecular mechanism leading to ischemic heart disease of the Japanese and for developing risk stratification and therapeutic strategy in terms of the order-made medicine. Specifically, research targets of this study were ischemic heart disease due to coronary atherosclerosis and one due to Japanese specific coronary vasospasm, and patients of these diseases were ascertained, and genomic DNAs were extracted from blood of them. Using these genomic DNAs, genetic analyses for identifying Japanese specific genetic factors leading to the pathogenesis of coronary atherosclerosis, restenosis after coronary intervention, and coronary vasospasm. By utilizing this information, the ultimate goal of this study was to develop the foundation of the order-made medicine for ischemic heart disease of the Japanese.To date, 171subjects of coronary atherosclerotic ischemic heart disease including one with coronary intervention … More (except drug eluting stent procedure) and 352 subjects of coronary vasospastic ischemic heart disease were ascertained. Clinical information and genomic DNAs were collected from these subjects.Since subjects for coronary vasospasm study were used as the control group for the analysis of coronary atherosclerosis, 17 gene polymorphisms were determined for all subjects of this study. Among these 17 genes, Lymphtoxin gene and other related ones that were reported to have an association with myocardial infarction of the Japanese, and Rho kinase gene and Paraoxonase 1 gene that we previously identified an association with coronary vasospasm were included.To date, no significant associations between phenotypes of interest, coronary atherosclerosis, restenosis after coronary intervention, and coronary vasospasm, and candidate genes studied. However, number of study subjects was relatively small, and number of candidate genes is limited. Therefore, it would be necessary to increase subjects and to carry out total genome scan for reaching the goal of this study in future. Less