MTHFR基因多态性与甲氨蝶呤不良反应的相关性研究  

Association of Genetic Polymorphisms of MTHFR and Methotrexate-related Adverse Reaction

作　　者：周新科[1] 舒文莹[1] 梁敏[1] 何璐[1] 

机构地区：[1]广州医科大学附属肿瘤医院,广东广州510095

出　　处：《中国药物警戒》2013年第11期647-649,共3页Chinese Journal of Pharmacovigilance

摘　　要：目的探讨采用大剂量甲氨蝶呤（MTX）化疗的癌症患者亚甲基四氢叶酸还原酶（MTHFR）c667T和A298C基因突变与MTX不良反应的相关性。方法收集大剂量MTX联合亚叶酸钙解救化疗方案的住院患者共102例，其中急性淋巴细胞白血病（ALL）患者62例，采用MTX1～3g／21d，24h静脉泵入；骨肉瘤患者40例，采用MTX8～10g／21d。采用实时荧光定量PCR法检测MTHFRC667T和A298C基因型。分析各基因型与不良反应的相关性。结果在ALL组发生不良反应的患者中，MTHR667TT基因型频率显著高于未发生不良反应组（34．1％和11．1％，P=0．025）。结论MTHRC667T多态性与MTX不良反应具有相关陛。Objective To investigate the association between methylentetrahydrofolate（MTHFR） C677T and A298C genetic polymorphisms and the adverse reaction aRer high-dose methotrexate（MTX） chemotherapy in Chinese cancer patients. Methods Total 102 inpadents receiving high-dose MTX chemotherapy were recruited in which the 62 acute lym- phoblasdc leukemia（ALL） patients were treated with 24h-intravenous injection of MTX 1- 3g/21d and the 40 osetosarcoma patients were treated with 24h-intrivenous injection of MTX 8 - 10g/21d. The genotype of MTHFR C667T and A298C was analyzed by real-time qPCR. The relation between genotypes and adverse reactions was ana- lyzed. Results The frequency ofMTHR 667TTwas significantly higher in ALL patients experienced adverse reaction than that in the ALL patients without adverse reaction（34.1% vs 11.1%, P =0.025）. Conclusion MTHR C667T genetic polymorphism was associated with MTX-related adverse reaction.

关 键 词：甲氨蝶呤 亚甲基四氢叶酸还原酶 基因多态性 不良反应 

分 类 号：R979.12[医药卫生—药品]