| Project/Area Number |
14207035
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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, Professor, 医学系研究科, 教授 (60107042)
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| Co-Investigator(Kenkyū-buntansha) |
KATSUYA Tomohiro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30311757)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥48,230,000 (Direct Cost: ¥37,100,000、Indirect Cost: ¥11,130,000)
Fiscal Year 2004: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2003: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2002: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
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| Keywords | gene polymorphism / disease susceptibility / cardiovascular disease / tailored medicine / hypertension / gene environmental interaction / salt sensitivity / obesity / 候補遺伝子 / SNPs / TaqMan / 薬剤反応性 / 環境・遺伝相互作用 / 対立遺伝子 / レニンーアンジオテンシン系 / レニン-アンジオテンシン系 |
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| Research Abstract |
Essential hypertension is a common disease and its cause is still unknown. Though the gene environmental interaction is important in the pathogenesis of essential hypertension, the precise mechanism of the interaction has not been elucidated yet. Using the candidate gene approach, we carried out several large genetic epidemiological studies (the Ohasama Study, the Suita Study and the Amagasaki Study) under the Ethics Guidelines of for Human/Genome/Gene analysis research, resulted that we revealed several gene environmental interactions. First of all, we pointed out the high frequency of salt sensitive alleles in Japanese than Caucasians according to the comparison in the allele frequency of angiotensinogen, alpha-adducin, aldosterone synthase and G protein beta 3 subunit gene polymorphisms. A genetic polymorphism of thiazide sensitive NaCl cotransporter gene, in which mutation was denoted as the genetic cause of Gitelman's syndrome, was also associated with the prevalence of essential hypertension only in females. In addition, methylenetetrahydrofolate reductase gene polymorphism increased the risk for carotid atherosclerosis in the females with smoking habit, and adiponectin gene polymorphism and hypoadiponectinemia were significantly associated with high prevalence of essential hypertension. The obtained results suggested the importance of personalized medication or life style modification according to the difference of their gene polymorphism. Furthermore, the infrastructure improvement of the genetic epidemiology that we developed is useful for future pharmacogenetic studies, such as HOMED-BP-GENE study.
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