2021 Fiscal Year Final Research Report
Development of a method for measuring the activity of the newly identified thiopurine metabolizing enzyme NUDT15
Project/Area Number |
19K08459
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Tohoku University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
角田 洋一 東北大学, 大学病院, 助教 (50509205)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | チオプリン製剤 / 薬理ゲノム / NUDT15 |
Outline of Final Research Achievements |
This study was conducted to develop a method to directly measure the activity of NUDT15, a thiopurine metabolizing enzyme. 6TGTP is metabolized by NUDT15, and the metabolite is 6TGMP, so a method to measure these was first developed. Then, erythrocytes were collected from subjects of each genotype, 6TGTP was added, and the metabolite 6TGMP was measured after a certain time, and differences by genotype could be detected. Although this showed that it was possible to compare the enzyme activities, the results varied greatly depending on the time and method of storage of the specimens, and the results varied more than the genotype differences.
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Free Research Field |
消化器内科学
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Academic Significance and Societal Importance of the Research Achievements |
古くから存在する免疫抑制剤であるチオプリン製剤は、炎症性腸疾患などの様々な疾患で現在も活用されている。日本人ではチオプリンを代謝する酵素であるNUDT15の遺伝子に複数のパターン(遺伝子型)が存在し、個人によって酵素の活性が大きく異なる。特に酵素の活性が極めて低いタイプ(日本人の1%)では白血球減少などの高度の副作用が発生する。現在NUDT15の遺伝子型検査が可能だが、特定の遺伝子多型しか検出できず未知の変異があった場合は検出されない。また、未知の変異が仮にあった場合、酵素活性がどう変わるかは不明であることから、直接酵素活性を測定可能であれば非常に有用である。
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