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Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on <i><scp>TPMT</scp></i> and <i><scp>NUDT</scp>15</i> Genotypes: 2018 Update
Clinical Pharmacology & Therapeutics · 2018 · Vol. 105(5) · pp. 1095–1105
Mary V. Relling(St. Jude Children's Research Hospital)Matthias Schwab(Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology)Michelle Whirl‐Carrillo(Stanford University)Guilherme Suarez‐Kurtz(Instituto Nacional de Câncer - INCA)Ching‐Hon Pui(St. Jude Children's Research Hospital)Charles Stein(Vanderbilt University)Ann M. Moyer(Mayo Clinic)William E. Evans(St. Jude Children's Research Hospital)Teri E. Klein(University of Tübingen)Federico Guillermo Antillon‐Klussmann(Universidad Francisco Marroquín)Kelly E. Caudle(St. Jude Children's Research Hospital)Motohiro Kato(National Center For Child Health and Development)Allen Eng Juh Yeoh(National University of Singapore)Kjeld Schmiegelow(University of Copenhagen)Jun J. Yang✉(St. Jude Children's Research Hospital)
Abstract
Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).
Acute Lymphoblastic Leukemia researchChildhood Cancer Survivors' Quality of LifeRetinoids in leukemia and cellular processesThiopurine methyltransferaseDosingPharmacogeneticsGuidelineGenotypeMedicinePharmacologyBiologyInternal medicineGenetics
MeSH terms
Pharmacogenomic TestingNudix HydrolasesAntimetabolites, AntineoplasticAzathioprineDose-Response Relationship, DrugHumansInactivation, MetabolicMethyltransferasesPharmacogeneticsPyrophosphatasesThioguanineMercaptopurineDrug Dosage Calculations
Funding
- Robert Bosch Stiftung
- National University of Defense Technology
- National Institutes of Health
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