MTHFR基因多态性与甲氨蝶呤不良反应的相关性研究

中国药物警戒 ›› 2013, Vol. 10 ›› Issue (11): 647-649.

MTHFR基因多态性与甲氨蝶呤不良反应的相关性研究

周新科,舒文莹^*,梁敏,何璐

广州医科大学附属肿瘤医院,广东广州 510095

收稿日期:2013-05-28 修回日期:2016-03-09 出版日期:2013-11-08 发布日期:2016-03-09
通讯作者: 舒文莹,女,博士,主管药师,药品不良反应监测。 E-mail:790840799@qq.com
作者简介:周新科,男,博士,主任医师,肿瘤治疗与临床合理用药监测。

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

ZHOU Xin-ke, SHU Wen-ying^* ,LIANG Min ,HE Lu

Cancer Hospital of Guangzhou Medical University, Guangdong Guangzhou 510095, China

Received:2013-05-28 Revised:2016-03-09 Online:2013-11-08 Published:2016-03-09

摘要/Abstract

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MTX 1～3g/21d,24h静脉泵入；骨肉瘤患者40例,采用MTX 8～10g/21d。采用实时荧光定量PCR 法检测MTHFR C667T 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,MTHR 667TT 基因型频率显著高于未发生不良反应组（34.1%和11.1%, =0.025）。结论 MTHR C667T 多态性与MTX 不良反应具有相关性。

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

Abstract: Objective To investigate the association between methylentetrahydrofolate (MTHFR) C677T and A298C genetic polymorphisms and the adverse reaction after high-dose methotrexate(MTX) chemotherapy in Chinese cancer patients. Methods Total 102 inpatients receiving high-dose MTX chemotherapy were recruited in which the 62 acute lymphoblastic leukemia ( ALL ) patients were treated with 24h -intravenous injection of MTX1～3g / 21d and the 40 osetosarcoma patients were treated with 24h -intravenous injection of MTX8～10g/21d. The genotype of MTHFR C667T and A298C was analyzed by real-time qPCR. The relation between genotypes and adverse reactions was analyzed. Results The frequency of MTHR 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.

Key words: methotrexate, methylentetrahydrofolate, genetic polymorphism, adverse reaction

中图分类号:

R979.12
R917

周新科,舒文莹,梁敏,何璐. MTHFR基因多态性与甲氨蝶呤不良反应的相关性研究[J]. 中国药物警戒, 2013, 10(11): 647-649.

ZHOU Xin-ke, SHU Wen-ying ,LIANG Min ,HE Lu. Association of Genetic Polymorphisms of MTHFR and Methotrexate-related Adverse Reaction [J]. Chinese Journal of Pharmacovigilance, 2013, 10(11): 647-649.

参考文献

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