亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤不良反应关系的Meta分析

Meta- analysis of methylenetetrahydrofolate reductase genetic polymorphisms and adverse drug reactions of methotrexate

目的评价中国人群亚甲基四氢叶酸还原酶(MTHFR)基因多态性与甲氨蝶呤(MTX)治疗急性淋巴细胞白血病不良反应的关联性。方法检索相关数据库,收集中国人群MTHFR C677T及A1298C基因多态性与甲氨蝶呤治疗急性淋巴细胞白血病不良反应关联性的病例对照研究,用Rev Man 5.3软件进行Meta分析。结果共纳入10篇文献,MTHFR C677T 10篇,A1298C 5篇。MTHFR677CC皮疹的发生风险低于677CT/TT(P<0.05),不良反应总发生率及其余各类型不良反应发生风险差异无统计学意义,年龄对该基因多态性与甲氨蝶呤不良反应关联性的影响不显著。MTHFR 1298AA与1298AC/CC相比,不良反应总发生率及各类型不良反应发生风险差异无统计学意义,但在儿童患者,MTHFR1298AA黏膜损害的发生风险低于1298AC/CC(P<0.05)。结论在中国人群中,MTHFR C677T及A1298C基因多态性可能不影响甲氨蝶呤治疗急性淋巴细胞白血病不良反应总发生率,但与部分不良反应类型(皮疹、黏膜损害)有一定的相关性。

Objective To investigate the relationship between methylenetetrahydrofolate reductase（ MTHFR） genetic polymorphisms and adverse drug reactions of methotrexate（ MTX） chemotherapy for acute lymphoblastic leukemia（ ALL） in China. Methods The relevant data bases were searched and reviewed. Meta- analysis was performed by software of RevMan 5. 3. Results Ten studies were included,and half of them only involved MTHFR C677 T,and the others involved both. The meta- analysis showed thatcompared with 677 CT / TT,677 CC had a lower risk of erythra（ P〈0. 05）; there were no significant differences in the total adverse drug reactions and other types of adverse drug reaction; age had no effect on the relationship between MTHFR genetic polymorphisms and adverse reactions of MTX. There were no significant differences in the total adverse reactions and different types of adverse reaction between1298 AA and 1298 AC / CC; 1298 AA had a lower risk of mucositis than1298 AC / CC in pediatric ALL（ P〈0. 05）. Conclusion MTHFR C677 T and A1298 C polymorphisms do not seem to be good markers of MTX- related total adverse drug reactions,but may affect part types such as erythra and mucositis in Chinese ALL.