基于 TPMT 和 NUDT15 基因型的硫嘌呤药物剂量调整：临床药物遗传学实施联盟指南 2018 年更新版。
Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update.
机构信息
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
出版信息
Clin Pharmacol Ther. 2019 May;105(5):1095-1105. doi: 10.1002/cpt.1304. Epub 2019 Jan 20.
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).
摘要
硫嘌呤甲基转移酶（TPMT）活性表现为单基因共显性遗传，可分解硫嘌呤。TPMT 变异等位基因与低酶活性和硫嘌呤的明显药理作用有关。NUDT15 基因的失活等位基因在亚洲人和西班牙裔中很常见，可减少活性硫嘌呤核苷酸代谢物的降解，也易导致骨髓抑制。我们根据 TPMT 和 NUDT15 基因型为巯嘌呤、硫鸟嘌呤和硫唑嘌呤推荐起始剂量调整（www.cpicpgx.org 上的更新）。
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