2000 Fiscal Year Final Research Report Summary
Identification of genetic susceptibility for cardiovascular disease : two large genetic epidemiological study with cohort base
| Project/Area Number |
10307018
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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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 | OSAKA UNIVERSITY |
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Principal Investigator |
OGIHARA Toshio Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Professor, 医学系研究科, 教授 (60107042)
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| Co-Investigator(Kenkyū-buntansha) |
MIKI Tetsuro Ehime University Medical, Department of Geriatric Medicine, Professor, 医学部, 教授 (00174003)
KATSUYA Tomohiro Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Assistant Professor, 医学系研究科, 助手 (30311757)
HIGAKI Jitsuo Osaka University Graduate School of Medicine, Department of Geriatric Medicine, Associate Professor, 医学系研究科, 助教授 (70189744)
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| Project Period (FY) |
1998 – 2000
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| Keywords | polymorphism / pharamacogenetics / renin-angiotensin system / SNPs / hypertension / cohort study / lacunar infarction / genetic susceptibility |
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| Research Abstract |
To identify causal genes of cardiovascular disease (hypertension, ischemic heart disease), we carried out a genetic investigation using candidate gene approach. In a cohort study using a large number of urban residents (S study), deletion/insertion polymorphism of angiotensin converting enzyme gene (ACE) was determined in 5,014 subjects. The deletion homozygote of ACE (ACE/DD) increased the risk for pertension with male specific manner in Japanese, which suggested the similarity in the obtained results between Japanese and Caucasians (Circulation, 2000). Another cohort study using a large number of subjects in a rural community in northern part of Japan (O study) showed a unique association between lacunar infarction or periventriular hyperintensity and angiotensinogen or angiotensin II type 1 receptor polymorphism. We also obtained several interesting results : GNB3 gene polymorphism was not associated with hypertension, and several polymorphisms were identified in the beta subunit of epithelial sodium channel gene. On the other hand, M235T polymorphism of angiotensinogen gene was not associated with plasma angiotensinogen concentration but with increased risk for essential hypertension, which suggested that the genotype-phenotype correlation did not directly reflect the expression level of angiotensinogen gene. In the pharmacogenetic investigation, ACE/DD attenuated the effect of antihypertensive therapy or improvement of restenosis of coronary artery after PTCA.We also proposed the advantage and disadvantage of the methods of genetic investigations.
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