药物遗传学
SLCO1B1型
医学
甲氨蝶呤
内科学
不良事件通用术语标准
不利影响
药理学
肿瘤科
基因型
基因
生物
遗传学
作者
О. D. Gurieva,Marina I. Savelyevа,Т. Т. Валиев,Zhannet A. Sozaeva,С. Н. Кондратенко,M. V. Ilyin
出处
期刊:Drug metabolism and personalized therapy
[De Gruyter]
日期:2023-12-01
卷期号:38 (4): 349-357
被引量:2
标识
DOI:10.1515/dmpt-2023-0079
摘要
Abstract Objectives To evaluate the role of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 genetic polymorphisms in the development of major types of methotrexate (MTX) toxicities and the occurrence of a terminal event (death, relapse) in pediatric АLL. Methods The study included 124 patients diagnosed with pediatric ALL. All patients treated according to the protocols of the German BFM group (2002/2009) with high-dose (1,000, 2,000 and 5,000 mg/m 2 ) methotrexate. MTX-related toxicities, including hematologic, hepatic and renal, were evaluated according to the common terminology criteria for adverse events version 5.0 (CTCAE v.5.0). Real-time PCR method was used to investigate polymorphisms of ABCB1 and SLCO1B1 genes. The study material was peripheral blood. Results A competitive analysis demonstrated significant relationships between MTX ADRs. The results of the study support the existence of relationships between some ADRs and MTX kinetics. An associative analysis showed association with the development of AEs to methotrexate indicating their clinical significance from different genetic polymorphisms protein-transporters. The available results confirm the associations of the studied genes with the increased risk of high doses MTX toxic ADRs and terminal events. Conclusions Complementing the existing criteria for pediatric ALL risk groups with pharmacogenetic indicators will allow further individualization of therapy.
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