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

• Project/Area Number: 18590818
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyushu University
• Principal Investigator: KOIKE George Kyushu University, Kyushu University Hospital, Visiting Lecturer (90325522)
• Co-Investigator(Kenkyū-buntansha): EGASHIRA Kensuke KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Associate Professor (60260379) ; TAKEMOTO Masao KYUSHU UNIVERSITY, Kyushu University Hospital, Assistant Professor (90403998)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: Ischemic heart disease / Coronary atherosclerosis / Restenosis after coronary intervention / Coronary vasospasm / Gene polymorphism / Genetic analysis

Research Abstract

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 (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.