DNA-Thioguanine Nucleotides as a Marker for Thiopurine Induced Late Leukopenia after Dose Optimizing by NUDT15 C415T in Chinese Patients with IBD

Autor: Xia Zhu, Kang Chao, Ting Yang, Xue‐ding Wang, Shaoxing Guan, Jian Tang, Wen Xie, Ai‐ming Yu, Qing fan Yang, Miao Li, Hong‐sheng Yang, Na Diao, Pin‐jin Hu, Xiang Gao, Min Huang
Rok vydání: 2022
Předmět:
Zdroj: Clinical pharmacology and therapeutics. 112(6)
ISSN: 1532-6535
Popis: Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence ( 2 months). Although laboratory monitoring of 6-thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells 3.5 × 10
Databáze: OpenAIRE