中国当代儿科杂志2025，Vol.27Issue(7)：802-807,6.DOI:10.7499/j.issn.1008-8830.2411059
MTHFR及GGH基因多态性对儿童急性淋巴细胞白血病大剂量氨甲蝶呤治疗后血药浓度及毒性的影响
Effects of MTHFR and GGH gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate therapy in children with acute lymphoblastic leukemia
滕琳霄 1徐淑梅 1史鲲鹏 1仇方珊 1杜惜惜 1拾金蕊 1安琪 1王磊 1王楠 1孔庆玲 1韩蕊 1王媛 1刘璐 1王岩1
作者信息
- 1. 徐州医科大学附属徐州儿童医院血液肿瘤内科,江苏 徐州 221002
- 折叠
摘要
Abstract
Objective To investigate the effects of methylenetetrahydrofolate reductase(MTHFR)rs1801133 and γ-glutamyl hydrolase(GGH)rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate(MTX)therapy in children with acute lymphoblastic leukemia(ALL).Methods Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study.Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction.MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique,and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0.The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed.Results In the low-risk ALL group,the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours(P<0.05).In the intermediate-to high-risk group,the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours(P<0.05),and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours(P<0.05).In the intermediate-to high-risk group,the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin(P<0.05),and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia(P<0.05).Conclusions Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL,enabling timely interventions to enhance safety.关键词
急性淋巴细胞白血病/氨甲蝶呤/亚甲基四氢叶酸还原酶/药物基因/毒性反应/儿童Key words
Acute lymphoblastic leukemia/Methotrexate/Methylenetetrahydrofolate reductase/Pharmacogenomics/Toxicity/Child引用本文复制引用
滕琳霄,徐淑梅,史鲲鹏,仇方珊,杜惜惜,拾金蕊,安琪,王磊,王楠,孔庆玲,韩蕊,王媛,刘璐,王岩..MTHFR及GGH基因多态性对儿童急性淋巴细胞白血病大剂量氨甲蝶呤治疗后血药浓度及毒性的影响[J].中国当代儿科杂志,2025,27(7):802-807,6.
