Molecular epidemiology of acute coronary syndrome in Japan : Large-scale, prospective, multicenter clinical investigation

日本急性冠状动脉综合征的分子流行病学：大规模、前瞻性、多中心临床研究

• 批准号: 11794035
• 负责人: HORI Masatsugu
• 金额: $ 11.71万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for University and Society Collaboration
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11794035/
• 关键词: Acute myocardial infarction; Large-scale, prospective, multicenter clinical investigation; DNA bank; Serum Bank; 多施設共同大規模臨床検査; DNA-バンク

In 2000, we performed (1) to examine the predictors of in-hospital mortality alter acute myocardial infarction, (2) to investigate the association between Chlamydia pneumoniae IgG and/or IgA antibodies and the onset of acute myocardial infarction and joint effects of Chlamydia pneumoniae infection and classic coronary risk factors on risk of acute myocardial infarction, and (3) to clarify genetic background in the pathogenesis of acute myocardial infarction.(1) Predictors of in-hospital morality alter acute myocardial infarctionWe showed that collateral vessel influences better in-hospital mentality and its effect is modified by aging, diabetes mellitus, and preinfarction angina.(2) The effect of Chlamydia pneumoniae infection on the onset of acute myocardial infarctionWe showed that the predictive value of Chlamydia pneumoniae IgA antibody titer for acute myocardial infarction is only weakly positive and of marginal statistical significance. However, the joint effects of high C pneumoniae IgA antibody titers together with classic coronary risk factors such as obesity, hypercholesterolemia, and smoking are greater.(3) The association between genetic background and the pathogenesis of acute myocardial infarctionWe performed a genome-wide association study using the high-throughout multiplex PCR-Invader assay method at 92,788 randomly selected gene-based singe-nucleotide polymorphisms (SNPs). We found that two SNPs were significantly associated with acute myocardial infarction. We are now making a dense SNP map of this locus for linkage disequilibrium mapping, followed by functional analyses of gene products.

在2000年，我们进行了（1）检查急性心肌梗死后院内死亡率的预测因素，（2）研究肺炎衣原体IgG和/或伊加抗体与急性心肌梗死发病的关系以及肺炎衣原体感染和经典冠状动脉危险因素对急性心肌梗死风险的联合作用，（3）阐明急性心肌梗死发病的遗传背景。(1)急性心肌梗死患者住院期间死亡率的预测因素我们发现，侧支血管对住院期间的死亡率有更好的影响，其影响会因年龄、糖尿病和梗死前心绞痛而改变。(2)肺炎衣原体感染对急性心肌梗死发病的影响我们发现肺炎衣原体伊加抗体滴度对急性心肌梗死的预测价值仅为弱阳性，且具有边缘统计学意义。然而，高肺炎衣原体伊加抗体滴度与典型的冠状动脉危险因素如肥胖、高胆固醇血症和吸烟的联合作用更大。(3)遗传背景与急性心肌梗死发病机制的关系我们使用高通量多重PCR-侵入分析方法对92，788个随机选择的基于基因的单核苷酸多态性（SNP）进行了全基因组关联研究。我们发现两个SNPs与急性心肌梗死显著相关。我们现在正在制作这个位点的高密度SNP图谱，用于连锁不平衡作图，然后对基因产物进行功能分析。

项目成果

Sanada S: "Cardioprotective effect afforded b transient exposure to phosphodiesterase III inhibitors : role of protein kinase A and p38 mitogen-activated protein kinase"Circulation. 104. 705-710 (2001)

Sanada S：“短暂暴露于磷酸二酯酶 III 抑制剂所产生的心脏保护作用：蛋白激酶 A 和 p38 丝裂原激活蛋白激酶的作用”循环。

大西洋三: "Identification of 187 Single Nucleotide Polymorphisms among 41 Candidate Genes for Ischemic Heart Disease In Japanese Population"Human Genetics. (in press).

大西洋：“日本人群缺血性心脏病 41 个候选基因中 187 个单核苷酸多态性的鉴定”人类遗传学（正在出版）。

黒飛俊哉: "高齢者急性心筋梗塞に対するdirect PTCAの有効性と安全性"日本心臓病学会. 34巻. 283 (1999)

Toshiya Kurotobi：“直接 PTCA 治疗老年人急性心肌梗死的疗效和安全性”日本心脏病学会第 34 卷 283（1999 年）。

Ohnishi Y: "A high-throughput SNP typing system for genome-wide association studies"Journal of Human Genetics. 46. 471-477 (2001)

Ohnishi Y：“用于全基因组关联研究的高通量 SNP 分型系统”人类遗传学杂志。

Sanada S: "Cardioprotective effect afforded by transient exposure to phosphodiesterase III inhibitors : the role of protein kinase A and p38 mitogen-activated protein kinase"Circulation. 104. 705-710 (2001)

Sanada S：“短暂暴露于磷酸二酯酶 III 抑制剂所产生的心脏保护作用：蛋白激酶 A 和 p38 丝裂原激活蛋白激酶的作用”循环。