ABCB1 C3435T基因多态性与甲氨蝶呤治疗儿童急性淋巴细胞白血病安全性Meta分析

Association between ABCB1 C3435T polymorphisms and methotrexate-induced toxicity in childhood acute lymphoblastic leukemia:Meta analysis

目的系统评价ABCB1 C3435T基因多态性与急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)儿童患者接受甲氨蝶呤(methotrexate,MTX)治疗安全性的相关性。方法检索PubMed、Science direct、中国知网、万方数据,时限均为建库至2020年3月31日。纳入13项研究,共1951例患者。采用RevMan 5.3软件进行Meta分析。结果Meta分析结果显示:与CC型比较,CT/TT型可增加MTX治疗ALL儿童患者肝损伤的发生[OR=2.36,95%CI(1.38~4.06),I^(2)=0%,P=0.002]。ABCB1 C3435T基因多态性对ALL儿童患者黏膜炎[OR=1.44,95%CI(0.94~2.19),I^(2)=25%,P=0.09]、胃肠道反应[OR=0.91,95%CI(0.54~1.54),I^(2)=0%,P=0.72]、骨髓抑制[OR=1.24,95%CI(0.42~3.67),I^(2)=74%,P=0.69]、肾功能不全[OR=0.51,95%CI(0.13~1.93),I^(2)=0%,P=0.32]、排泄延迟[OR=1.05,95%CI(0.38~2.90),I^(2)=0%,P=0.92]、24 h[SMD=0.49,95%CI(-0.59~1.57),I^(2)=83%,P=0.37]和42 h[SMD=0.03,95%CI(-0.40~0.47),I^(2)=0%,P=0.88]MTX浓度的影响差异无统计学意义。结论ABCB1 C3435T基因突变会增加MTX治疗ALL儿童肝损伤的发生,ABCB1 C3435T基因多态性对黏膜炎、胃肠道反应、骨髓抑制、肾功能不全、排泄延迟、MTX血浆水平等无影响。

Objective To study the correlations between ABCB1 C3435T genetic polymorphisms and the safety of MTX in pediatric ALL.Methods PubMed,Science direct,CNKI,and Wanfang database were searched for the most eligible studies published from the inception to March 2020.Meta analysis was performed using RevMan 5.3 software.Results A total of 13 studies were included involving 1951 patients.Meta-analysis results showed that CT/TT genetype increased the chance of hepatotoxicity in pediatric ALL compared with CC genetype[OR=2.36,95%CI(1.38~4.06),I^(2)=0%,P=0.002].There was no association between ABCB1 C3435T genetic polymorphisms and mucositis[OR=1.44,95%CI(0.94~2.19),I^(2)=25%,P=0.09],gastrointestinal reaction[OR=0.91,95%CI(0.54~1.54),I^(2)=0%,P=0.74],myelosuppression[OR=1.24,95%CI(0.42~3.67),I^(2)=74%,P=0.69],renal insufficiency[OR=0.51,95%CI(0.13~1.93),I^(2)=0%,P=0.32],excretion delay[OR=1.05,95%CI(0.38~2.90),I^(2)=0%,P=0.92],24 h[SMD=0.49,95%CI(-0.59~1.57),I^(2)=83%,P=0.37]and 42h[SMD=0.03,95%CI(-0.40~0.47),I^(2)=0%,P=0.88]MTX concentrations in children with ALL.Conclusion ABCB1 C3435T genetic mutations can increases the incidence of hepatotoxicity in pediatric ALL.The genetic polymorphism of ABCB1 C3435T has no effect on mucositis,gastrointestinal reactions,myelosuppression,renal insufficiency,excretion delay or plasma levels of MTX.