2022 Fiscal Year Final Research Report
Exploring the molecular mechanism and the clinical features of carriers with a variant of a high-risk disease-associated gene of type 2 diabetes mellitus
| Project/Area Number |
19K11723
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 59040:Nutrition science and health science-related
|
|---|
| Research Institution | Kyorin University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
粟崎 健 杏林大学, 医学部, 教授 (60359669)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Keywords | type 2 diabetes mellitus / TBC1D4 / pollux / drosophila |
|---|
| Outline of Final Research Achievements |
A common nonsense variant in TBC1D4 was known to substantially increase the risk of type 2 diabetes in Greenlandic Inuit. The nonsense variant is extremely rare in the world without Inuit population. We found a Japanese family carrying this variant independently, and four heterozygous carriers among a Japanese cohort study. None of the carriers we studied had diabetes at the time of the study. We focused on the pollux (plx) gene, the Drosophila ortholog of TBC1D4, and analyzed its function at the cellular and individual levels. Our results suggest that plx mutation does not significantly affect development of brain/nervous system and skeletal muscle, that the plx gene may be related to starvation tolerance, and that plx affects the expression and subcellular localization of sugar transporters.
|
| Free Research Field |
Neurology
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では、北極圏に住む2型糖尿病の発症に強く寄与するTBC1D4遺伝子のナンセンスバリアントを持つ日本人がいることを見出した。食生活の変化とともに2型糖尿病の罹患率が急増しているという共通の背景を持つ両者において、今後、糖尿病を含めた代謝異常の予防や個別化医療に発展する可能性があり、社会的意義があると考える。また、本研究によりショウジョウバエをモデルとした解析系を確立することができたことで、北極圏におけるTBC1D4遺伝子のナンセンスバリアントが潜在的に有する生物学的意義についても実験的に解析することが可能となった。このことは学術的意義が高いと考える。
|
