Grant-in-Aid for Scientific Research on Priority Areas
|Allocation Type||Single-year Grants |
|Research Institution||Ehime University |
MIKI Tetsuro Ehime University School of Medicine, Department of Geriatric Medicine, Professor, 医学部, 教授 (00174003)
KOHARA Katsuhiko Ehime University School of Medicine, Department of Geriatric Medicine, Associate Professor, 医学部, 助教授 (30260384)
NAKURA Jun Ehime University School of Medicine, Department of Geriatric Medicine, Lecturer, 医学部附属病院, 講師 (70304607)
TABARA Yasuharu Ehime University School of Medicine, Department of Geriatric Medicine, Assistant, 医学部, 講師 (00268749)
|Project Period (FY)
2000 – 2004
Completed (Fiscal Year 2004)
|Budget Amount *help
¥92,800,000 (Direct Cost: ¥92,800,000)
Fiscal Year 2004: ¥23,000,000 (Direct Cost: ¥23,000,000)
Fiscal Year 2003: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2002: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2001: ¥25,000,000 (Direct Cost: ¥25,000,000)
|Keywords||hypertension / atherosclerosis / single nucleotide polymorphism / gene-environmental interaction / 循環器疾患 / 感受性遺伝子 / SNP / ケース / コントロール / 動脈硬化関連遺伝子 / 高血圧関連遺伝子 / 多型 / オッズ比 / 95%信頼限界 / 相互作用解析 / マイクロサテライトマーカー / 遺伝子 / 相互作用 / ゲノムワイドスキャニング / SNPs|
In the present study, we explored susceptible genes for the development of hypertension and atherosclerosis by the genome-wide systemic candidate gene screening. A susceptibility of the already-known candidate genes was also re-evaluated. The genome-wide screening was carried out using 1,400 hypertensive/normotensive subjects. The validity of screened genes, as well as already-known candidate genes, was assessed using 11,000 community-based Japanese subjects colleted from the nation-wide. To explore the susceptibility of genes for multi-factorial disease, a gene-environmental interaction was considered in the analysis.
1. large-scale genetic epidemiological study cohort
In addition to the own recruitment, the study subjects were collected from the nation-wide in collaboration with other investigators. A total number of 11,000 subjects having detailed clinical information were finally collected.
2. case-control subjects
Approximately 1400 of hypertensive and normotensive subjects (700 subje
cts each) were collected from the nation-wide for the purpose of screening of candidate genes.
3. high-throughput genotyping system
A high-throughput genotyping system which can determine more than 12,000 genotypes per day was constructed.
4. genome-wide candidate gene screening
A susceptibility of approximately 300 SNPs locating in genes encoding the components of signal transduction system were evaluated using the case/control subjects, and the 38 SNPs showed statistically significant. Validity of these positive SNPs was evaluated using the large-scale Japanese subjects.
5. gene-environmental interaction
The already-known candidate genes for hypertension were re-analyzed by the view of gene-environmental interaction. Although marked direct association was not observed in any gene, several genes showed significant association with the interaction with other environmental factors.
The accumulation of these evidences contributes to clarify the genetic background of hypertension and atherosclerosis. Less