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目的探讨急性淋巴细胞白血病(ALL)患儿中亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点的多态性与甲氨蝶呤(MTX)毒副反应的相关性。方法通过检索Pub Med、Cochrane Library、Web of Science、Embase等数据库,收集建库至2016年8月1日关于ALL患儿M THFR C677T位点的多态性与M TX毒副反应的观察性队列研究,并提取基因型、MTX毒性相关资料进行方法学质量评价,采用Rev Man 5.3软件进行M eta分析。结果共纳入9篇文献进行M eta分析,结果显示,M THFR C677T多态性与肝毒性(如:CC vs.CT/TT,RR:0.81,95%CI:0.65~1.00,P=0.05)、血液毒性、黏膜毒性均不存在显著相关性。但单个研究显示,非洲人群在肝毒性、血液毒性、黏膜毒性(如:CC/CT vs.TT,RR:0.10,95%CI:0.03~0.39,P=0.000 9)方面,677C等位基因相对于其他人种而言具有较明显的保护作用。结论在ALL患儿中,MTHFR C677T不是一个好的预测MTX毒性的指标,两者的关系尚需要大样本量、高质量的研究来进一步验证。
Objective To investigate the association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T and the toxicity of methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). Methods The databases of Pub Med, Cochrane Library, Web of Science and Embase were searched to collect the observational cohort of MTHFR C677T polymorphism and M TX toxicities in children with ALL until August 1, 2016 The genotypes and MTX toxicity-related data were extracted for methodological quality evaluation, and RevMan 5.3 software was used for M eta analysis. Results A total of 9 articles were included in the M eta analysis. The results showed that M THFR C677T polymorphism and hepatotoxicity (eg CC vs. CT / TT, RR: 0.81, 95% CI: 0.65-1.00, P = 0.05) There was no significant correlation between hematologic toxicity and mucosal toxicity. However, in a single study, the 677C allele was negatively correlated with hepatotoxicity, hematologic toxicity, mucosal toxicity (eg CC / CT vs. TT, RR: 0.10, 95% CI: 0.03-0.39, P = 0.0009) In terms of other ethnic groups have a more obvious protective effect. Conclusions MTHFR C677T is not a good predictor of MTX toxicity in children with ALL, yet the relationship between the two needs large sample size and high quality studies to further validate the relationship.