| Project/Area Number |
13204050
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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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)
檜垣 實男 大阪大学, 医学系研究科, 助教授 (70189744)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥35,600,000 (Direct Cost: ¥35,600,000)
Fiscal Year 2004: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2002: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | gene polymorphism / disease susceptibility / cardiovascular disease / personalized medicine / hypertension / gene environmental interaction / salt sensitivity / obesity / 対立遺伝子 / SNPs / 高血圧 / ゲノムスキャン / 環境・遺伝相互作用 / TaqMan / レニン-アンジオテンシン系 / 環境・遺伝子相互作用 |
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| Research Abstract |
Essential hypertension is major risk for cardiovascular 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. To demonstrate the whole genome scan, we provided a lot of number of human DNA samples (n>10,000) to Hypertension Task Force of Japanese Millennium Genome Project, resulted that several new candidate genes were identified. Using the candidate gene approach, we carried out Handai Study and several large genetic epidemiological studies (S, O, A, TS), resulted that we also 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 AGT, ADD1, GNB3, CYP11B2 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, MTHFR polymorphism increased the risk for carotid atherosclerosis in the females with smoking habit, and ADRB2and ET1 gene polymorphisms were significantly associated with high prevalence of essential hypertension with obesity. The obtained results suggested the importance of personalized medication or life style modification according to the difference of their gene polymorphism.
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