2023 Fiscal Year Final Research Report

The impact of the NUDT15 variant in adverse effects occurring in infants born to pregnant women taking thiopurine

Research Project

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Project/Area Number	19K07113
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 47040:Pharmacology-related
Research Institution	Osaka Medical and Pharmaceutical University (2020-2023) Hyogo Medical University (2019)
Principal Investigator	Nakamura Shiro 大阪医科薬科大学, 医学部, 教授 (50271185)
Co-Investigator(Kenkyū-buntansha)	佐藤寿行兵庫医科大学, 医学部, 助教 (20836225) 渡辺憲治兵庫医科大学, 医学部, 非常勤講師 (70382041)
Project Period (FY)	2019-04-01 – 2024-03-31
Keywords	NUDT15 / チオプリン / 遺伝子多型検査 / 潰瘍性大腸炎 / クローン病 / 炎症性腸疾患 / 遺伝薬理学 / ファーマコゲノミクス
Outline of Final Research Achievements	When pregnant women take thiopurine (IM), depending on the NUDT15 gene variant, the fetus may suffer from dangerous conditions such as myelosuppression, and the adverse effects in infants born to pregnant women taking IM were investigated. Eleven participants in the prospective study were still taking IM at birth, and no adverse effects such as leukaemia were observed in the newborns, regardless of the NUDT15 genotype. 6-TGN levels were found to be low in the newborns, although they were transferred at about 1/3 of the mother's level. In the retrospective study, 12 patients were examined, and although many of the postnatal details were unknown due to patient transfers, etc., no major adverse effects were observed in the children as far as the study was concerned. Further studies with larger scale surveys are required in the future.
Free Research Field	炎症性腸疾患
Academic Significance and Societal Importance of the Research Achievements	NUDT15遺伝子多型検査が保険適用となりチオプリン製剤をより安全に使える時代となった。しかしながら炎症性腸疾患のような若年者に多く、妊娠可能年齢で発症する疾患では、母が比較的安全に服用可能なgenotypeを保有していても、児が副作用の多いgenotypeを保有し、重篤な副作用をもち出生してくることはありうる。胎児やパートナー男性のgenotypeを調べる検査は保険適用でなく、その中でどのように妊娠中の母の原疾患を良好な状態で維持していくか担当医は注意を払う必要がある。今後NUDT15のように副作用回避に有用なゲノムバイオマーカーが見つかった際にも本研究は参考になると思われる。