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Thiopurine 약물치료에 있어서 NUDT15 유전형 검사

NUDT15 Genotyping in Thiopurine Drug Therapy

이수연|최리화|이종권
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2022.10|Laboratory Medicine Online|제12권 제4호|pp. 217-226|DOI 10.47429/lmo.2022.12.4.217

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키워드

GuidelineGenotypePharmacogeneticsThiopurineNUDT15

초록

티오퓨린 약물은 염증성 장질환, 백혈병, 종양, 자가면역질환, 이식 후 면역억제제 등 다양한 질환에서 치료제로 이용되는 전구약물이다. 티오퓨린 약물은 체내에서 여러 단계에 걸친 매우 다양한 효소에 의해 활성형 대사체로 대사된다. NUDT15 유전자 변이와 티오퓨린 약물의 치명적인 부작용인 혈구감소증이나 간독성, 탈모 등의 연관성이 밝혀져, 다양한 진료 지침과 문헌에서 NUDT15 유전자 검사의 중요성이 제시되고 있다. 이에 본 종설에서는 티오퓨린 치료를 받는 한국인 환자에서 임상적 중요성이 큰 NUDT15 약물유전형 검사를 임상검사실에서 시행함에 있어 실질적으로 도움이 될 수 있는 정보를 제공하고자 하였다. 본 종설에서는 티오퓨린 약물 대사, NUDT15 유전자의 임상적 의미와 유전형 및 표현형, NUDT15 유전형에 근거한 티오퓨린 적정약물요법 권고안을 포함하여 NUDT15 약물유전형 검사 결과 보고 시 고려해야하는 사항에 대해 중점을 두었다.

Abstract

Thiopurine is a pro-drug used to treat patients with inflammatory bowel disease, leukemia, malignancies, and autoimmune diseases as well as an immunosuppressive agent for post-transplantation states. Thiopurine drugs are metabolized into active metabolites by enzymes in various metabolic stages in the body. The importance of NUDT15 genotyping is emerging in the literature and clinical guidelines since it has been found to be associated with fatal thiopurine-related adverse drug reactions such as cytopenia, hepatotoxicity, and hair loss. Therefore, this review provides practical information about the clinical pharmacogenetic test for NUDT15 in patients treated with thiopurines to assist clinical laboratories in Ko rea. It focuses on thiopurine drug metabolism, clinical implications, and of NUDT15 genotyping. Moreover, it considers reports of pharmacogenetic test results, including current recommendations on NUDT15-guided thiopurine dosing.

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NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia구홍회, 성기웅, 유건희, 이나희, 이수연, 이은상, 이지원, 최리화, 최영배대한암학회 · Cancer Research and Treatment2018 · 제50권 제3호Prevention of thiopurine-induced early leukopenia in a Korean pediatric patient with Crohn’s disease who turned out to possess homozygous mutations in NUDT15 R139C강빈, Byung-Ho Choe, Jaewoan Bae영남대학교 의과대학 · Journal of Yeungnam Medical Science2020 · 제37권 제4호Successful Azathioprine Treatment with Metabolite Monitoring in a Pediatric Inflammatory Bowel Disease Patient Homozygous for TPMT*3C강빈, 김종원, 우혜인, 이미나, 이수연, 이유민, 최연호연세대학교의과대학 · Yonsei Medical Journal2013 · 제54권 제6호Quantification of Thioguanine in DNA Using Liquid Chromatography-Tandem Mass Spectrometry for Routine Thiopurine Drug Monitoring in Patients With Pediatric Acute Lymphoblastic Leukemia이수연, 이지원, Cho Hee Won, Choi Rihwa, Chun Mi Ryung, Hyun Ju Kyung, Ju Hee Young, Koo Hong Hoe, Park Jisook, Yi Eun Sang대한진단검사의학회 · Annals of Laboratory Medicine2021 · 제41권 제2호APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia강형진, 김주한, 김혜리, 민병주, 박경덕, 박유미, 서명의, 서희원, 신희영대한암학회 · Cancer Research and Treatment2018 · 제50권 제3호임상약물유전학 검사와 적용: 진단검사의학 임상검사 지침 - 1부김솔잎, 김인숙, 송상훈, 우혜인, 윤여민, 이경아, 이수연, 이우창, 전사일, 조현정, 지미숙, 채효진대한진단검사의학회 · Laboratory Medicine Online2016 · 제6권 제3호

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