Elucidation of the cause of diabetes in the Japanese population using whole genome information and development of diagnostic and therapeutic methods using iPS cells
| Project/Area Number |
18H04053
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
岩部 真人 東京大学, 医学部附属病院, 講師 (30557236)
岩部 美紀 東京大学, 医学部附属病院, 特任准教授 (70392529)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2020: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
|
|---|
| Keywords | 遺伝因子機能解析 |
|---|
| Outline of Final Research Achievements |
AFunctional analysis of variants of the type 2 diabetes susceptibility gene region was performed. It was shown that two different variants of the same gene region could regulate the expression of different genes in different tissues (Nature 2020). As a result of performing chromatin immunoprecipitation sequence and evaluating which transcription factor binding site the variant accumulates, FOXA2 and the like were found (Nat Genet 2020). We have shown that the GP2 variant can be a molecular mechanism for both type 2 diabetes and pancreatic cancer (Nat Commun 2020). When an Asian characteristic variant was expressed in pancreatic β-cells, GLP-1R altered insulin secretion (Nat Genet 2019) and PAX4 showed abnormal expression of endoplasmic reticulum calcium chaperone (HGV 2021). Genome editing was added to iPS cells, and functional analysis of variants in diabetic target cells was also performed (unpublished).
|
| Academic Significance and Societal Importance of the Research Achievements |
2型糖尿病とその合併症の発症・進展には遺伝因子の影響が極めて大きいにも関わらず、これまで大部分は未解明であった。また糖尿病の表現型は、欧米人と東アジア人で極めて異なるのに、これまで欧米主導で原因遺伝子探索が行われてきた。本研究は、史上初めて欧米を凌駕する糖尿病サンプル数を用いて行ったゲノムワイド関連解析の結果を基に、インスリン分泌が少なく、顕著に肥満しない場合にも糖尿病を発症する東アジア人の原因となる遺伝素因とその分子機序を明らかにしたことより、学術的意義は極めて高い。世界の1/3を占めるアジア人型の糖尿病の発症・進展予測と予防・治療法開発に直結する研究成果であり社会的意義も極めて高い。
|
Report
(4 results)
Research Products
(53 results)
-
-
-
[Journal Article] Identification of type 2 diabetes loci in 433,540 East Asian individuals.2020
Author(s)
Spracklen, C.N., Horikoshi, M., Kim, Y.J., Lin K, Bragg F, Nakatochi M, et al.
-
Journal Title
Nature
Volume: 印刷中
Pages: 240-245
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.2020
Author(s)
Yingsong, Lin., Doki, Y., Ishii, Hideshi, Eguchi, H., Mori, Masaki, Matsuo, K.
-
Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 3175-3175
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Prolyl hydroxylase domain inhibitor protects against metabolic disorders and associated kidney disease in obese type 2 diabetic mice.2020
Author(s)
Sugahara M, Tanaka S, Tanaka T, Saito H, Ishimoto Y, Wakashima T, Ueda M, Fukui K, Shimizu A, Inagi R, Yamauchi T, Kadowaki T, Nangaku M
-
Journal Title
J. Am. Soc. Nephrol.
Volume: 31
Pages: 560-577
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] Critical role of SREBP-1c large-VLDL pathway in environment-induced hypertriglyceridemia of apo AV deficiency.2019
Author(s)
Takanashi M, Kimura T, Li C, Tanaka M, Matsuhashi A, Yoshida H, Noda A, Xu P, Takase S, Okazaki S, Iizuka Y, Kumagai H, Ikeda Y, Gotoda T, Takahashi M, Yagyu H, Ishibashi S, Yamauchi T, Kadowaki T, Liang G, Okazaki H.
-
Journal Title
Arterioscler. Thromb. Vasc. Biol.
Volume: 39
Pages: 373-386
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Identification of 28 novel susceptibility loci for type 2 diabetes in the Japanese population2019
Author(s)
Suzuki K, Akiyama M, Horikoshi M, Kamatani Y, Hosoe J, Shojima N, Ishigaki K, Kanai M, Atsushi H, Kadota A, Kuriki K, Naito M, Tannno K, Ishigaki Y, Hirata M, Matsuda K, Iwata N, Ikeda M, Sawada N, Yamaji T, Iwasaki M, Ikegawa S, Okada Y, Maeda S, Murakam
-
Journal Title
Nature Genetics
Volume: 51
Issue: 3
Pages: 379-386
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4- indeuced M2asubtype macrophage activation in obesity.2018
Author(s)
Kubota T, Inoue M, Kubota N, Takamoto I, Mineyama T, Iwayama K, Tokuyama K, Moroi M, Ueki K, Yamauchi T, Kadowaki T
-
Journal Title
Nature Communications
Volume: 9
Pages: 4863-4863
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
