还原性叶酸载体1 G80A基因多态性与急性淋巴细胞白血病患儿使用大剂量甲氨蝶呤不良反应关系的系统评价

Systematic Review of Correlation between Polymorphism of Reduced Folate Carrier 1 G80A Gene and Adverse Drug Reactions of High-Dose Methotrexate in Children with Acute Lymphoblastic Leukemia

目的:探讨还原叶酸载体1(reduced folate carrier 1,RFC1)G80A基因多态性与儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者使用大剂量甲氨蝶呤(high dose methotrexate,HDMTX)化疗后不良反应的关系。方法:计算机检索PubMed、Cochrane图书馆和EMBase等数据库,收集RFC1G80A基因多态性与ALL患儿使用HDMTX化疗后发生不良反应的相关性研究,纳入符合标准的临床研究文献,提取有效数据,采用Rev Man 5.3软件对数据进行分析,比较不同RFC1G80A基因型ALL患儿使用HDMTX的不良反应发生情况。结果:共纳入英文文献6篇,Meta分析结果显示,RFC1G80A AA型患儿使用HDMTX的不良反应发生率高于RFC1G80A GA+RFC1G80A GG型患儿,差异具有统计学意义(OR=1.28,95%CI=1.00~1.63,P=0.05)。结论:RFC1G80A基因多态性与HDMTX的不良反应具有统计学意义的相关性。由于本研究纳入的文献数量有限,因此需要谨慎对待评价结果,尚需更多设计更合理、大样本量和多中心的临床对照研究进一步证实。

OBJECTIVE:To investigate the correlation between polymorphism of reduced folate carrier 1 G80 A(RCF1 G80 A)gene and adverse drug reactions of high-dose methotrexate(HDMTX)in children with acute lymphoblastic leukemia(ALL).METHODS:PubMed,the Cochrane Library,EMBase were retrieved to collect the related studies with correlation between RCF1 G80 A gene and adverse drug reactions of HDMTX in children with ALL.Clinical literature that met the standards was included,and effective data were extracted.RevMan 5.3 software was used to analyze the data and compare the incidence of adverse drug reactions of HDMTX in children with different RFC1 G80 A genotypes of ALL.RESULTS:A total of 6 English literature were included.Meta-analysis results showed that the incidence of adverse drug reactions of HDMTX in children with RFC1 G80 A AA type was higher than that in children with RFC1 G80 A GA+RFC1 G80 A GG type,with statistically significant difference(OR=1.28,95%CI=1.00-1.63,P=0.05).CONCLUSIONS:The polymorphism of RFC1 G80 A gene was significantly correlated with the adverse drug reactions of HDMTX.Due to the limited number of literature included in this study,the evaluation results need to be treated with caution,and more clinical controlled studies with more rational designs,large sample sizes,and multicenters are required for further confirmation.