2023 Fiscal Year Final Research Report
The development of in vitro functional assay system for the genetic variants in inherited autoinflammatory diseases.
| Project/Area Number |
21K07770
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | 自己炎症性疾患 / 遺伝子変異 |
|---|
| Outline of Final Research Achievements |
The aim of this study was to establish an experimental system for the evaluation of variants of unknown pathological significance in the recently discovered genes responsible for hereditary autoinflammatory diseases, namely the IL36RN, TNFAIP3, PSMB9, SAMD9L and IKBKG genes. This study has established an in vitro experimental system for the evaluation of genetic variants detected in patients using cultured cells of the HEK293 lineage without the use of patient-derived biological samples. On the other hand, with regard to the analysis of the IL-36 ligand-receptor complex structure, it was confirmed that the IL-36Ra protein can functionally inhibit the activity by IL-36α, but the creation of an IL-36 receptor protein that retains the ability to bind to the ligand remains an issue.
|
| Free Research Field |
小児科学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究により、IL36RN, TNFAIP3, IKBKG, PSMB9, SAMD9Lそれぞれの遺伝子のバリアントの病的意義の判定を行う、in vitro実験系が構築できた。今後、別途実施中あるいは実施予定の全国症例実態調査や新規に発生した疑い症例で見出された病的意義不明遺伝子バリアントについて、本法を用いることで患者由来生体試料を用いることなく病的意義の判定が可能となった。適切な確定診断を行うことで、効果的な治療を行うことにつながると考えられる。
|
