2005 Fiscal Year Final Research Report Summary
Identification of genetic factors responsible for the pathogenesis of coronary vasospasm, that is more prevalent in the Japanese, resulting in ischemic heart disease, and characterization of its molecular mechanism.
| Project/Area Number |
16590696
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KOIKE George Kyushu University, Hospital, Department of Cardiovascular Medicine, Assistant Professor, 大学病院, 講師 (90325522)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKI Toshihiro Kyushu University, Hospital, Department of Cardiovascular Medicine, Research Associate, 大学病院, 助手 (80311843)
SHIMOKAWA Hiroaki Tohoku University, Graduate School of Medicine, Medical Sciences, Professor, 大学院・医学系研究科, 教授 (00235681)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Ischemic heart disease / Coronary vasospasm / Genetic analysis / Single nucleotide polymorphisms / ROCK2 / PON1 |
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| Research Abstract |
It is well known that there are two major causes for ischemic heart disease, such as myocardial infarction. One is coronary atherosclerosis, and another is coronary vasospasm. Previous studies have demonstrated a significantly higher prevalence of coronary vasospasm in the Japanese than in Caucasians, suggesting an important role of genetic factors in the pathogenesis of coronary vasospasm. The specific aims of this study are (1)to identify genetic factors responsible for the pathogenesis of coronary vasospasm in the Japanese, and (2)to characterize its molecular mechanism based on genetic factors identified. For the specific aim 1, three groups of patients have bees ascertained, vasospastic angina (VSA) group (n=162), microvascular angina (MVA) group (n=61), and non-responder (NR, control) group (n=61). An association study was carried out with eight candidate genes with these patients. Two gene mutation/polymorphism were associated with coronary vasospasm, ROCK2 (Rho kinease gene) G930T and PON1 (paraoxonase 1 gene) A632G. ROCK2 G930T mutation that we have identified previously could alter the function by missense mutation. In this study, we have demonstrated that this mutation increased Rho kinase activity, possibly resulting in vasospasm. Regarding PON1 A632G polymorphism, we have reproduced an association between this polymorphism and VSA as described previously by Ito et al. In addition, this polymorphism was associated with MVA. This finding is novel. An association with VSA was in dominant fashion, and that with MVA was in recessive fashion, indicating that mechanism leading to vasospasm with PON1 A632G polymorphism could be different between VSA and MVA. This study is still on going, and further analysis is necessary to reach our goal.
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Research Products
(2 results)
