急性淋巴细胞白血病患儿亚甲基四氢叶酸还原酶基因C677T多态性与甲氨蝶呤毒副反应的研究  

Polymorphism C677T in methylenetetrahydrofolate reductase gene and its relationship to methotrexate-induced toxicities of childhood acute lymphoblastic leukemia

作　　者：李天媛[1] 王斌[2] 徐康康[1] 许静[1] 顾海娟[3] 廖清船[1] 杨力[4] 严宏力 

机构地区：[1]南京医科大学附属南京儿童医院药剂科,江苏南京210008 [2]南京医科大学基础医学院药理学系,江苏南京210029 [3]南通市肿瘤医院药剂科,江苏南通226361 [4]南京医科大学第一附属医院普外科,江苏南京210029 [5]安徽省东至卫生监督所,安徽东至247200

出　　处：《南京医科大学学报（自然科学版）》2010年第3期386-389,404,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省卫生厅医学科技发展基金临床药学科研项目(NO200706);江苏省高校自然科学基础研究面上项目(08KJB320004)

摘　　要：目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与甲氨蝶呤对急性淋巴细胞白血病患儿所致毒副反应的关系。方法:筛选急性淋巴细胞白血病患儿98例,运用PCR-RFLP方法分析亚甲基四氢叶酸还原酶基因型,分析此基因型与甲氨蝶呤临床毒副作用的关系。结果:携有突变基因型的患者甲氨蝶呤血药浓度高,发生毒副反应的风险大。结论:MTHFRC677T多态性与ALL患儿大剂量甲氨蝶呤化疗后的毒副作用有关,主要表现为胃肠道反应和骨髓抑制。Objective：To investigate the association between MTHFR C677T polymorphism and toxicities of methotrexate-induced toxicities of childhood acute lymphoblastic leukemia. Methods：A total of 98 children with acute lymphoblastic leukemia were selected. And PCR-RFLP was used to determine the genotypes of MTHFR C677T polymorphism. The toxicity response of patients received high-dose methotrexate chemotherapy was observed. Results：Compared with the wild-type CC,the carries of the variant genotypes （CT and TT） had higher methotrexate plasma concentration. Conclusion：MTHFR C677T polymorphism is associated with the toxicities of methotrexate-induced toxicities of childhood acute lymphoblastic leukemia,mainly gastrointestinal reaction and bone marrow suppression.

关 键 词：甲氨蝶呤 亚甲基四氢叶酸酶 基因多态性 毒副作用 

分 类 号：R733.71[医药卫生—肿瘤]