中国药物警戒 ›› 2022, Vol. 19 ›› Issue (4): 421-425.
DOI: 10.19803/j.1672-8629.2022.04.17

• 安全与合理用药 • 上一篇    下一篇

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

李宇1, 樊晖晖1, 冯晓俊2, 张永煌3, 陈琴1, 王运红1, 陈传涛1, 张蕾2, 史天陆2,*   

  1. 1太和县人民医院,安徽 阜阳 236600;
    2中国科学技术大学附属第一医院（安徽省立医院）,安徽 合肥 230001;
    3合肥市滨湖医院,安徽 合肥 230601
  • 收稿日期:2020-06-03 出版日期:2022-04-15 发布日期:2022-04-15
  • 通讯作者: *史天陆,男,主任药师,博士,药物基因组学。E-mail：tianlu828@163.com
  • 作者简介:李宇,男,药师,硕士,药物基因组学。
  • 基金资助:
    科大新医学联合基金（WK9110000079）

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

LI Yu1, FAN Huihui1, FENG Xiaojun2, ZHANG Yonghuang3, CHEN Qin1, WANG Yunhong1, CHEN Chuantao1, ZHANG Lei2, SHI Tianlu2,*   

  1. 1Taihe County People's Hospital, Fuyang Anhui 236600, China;
    2The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei Anhui 230001, China;
    3Binhu Hospital of Hefei, Hefei Anhui 230601, China;
  • Received:2020-06-03 Online:2022-04-15 Published:2022-04-15

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摘要： 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1 951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）,I2=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）,I2=25%,P=0.09]、胃肠道反应[OR=0.91,95%CI（0.54~1.54）,I2=0%,P=0.72]、骨髓抑制[OR=1.24,95%CI（0.42~3.67）,I2=74%,P=0.69]、肾功能不全[OR=0.51,95%CI（0.13~1.93）,I2=0%,P=0.32]、排泄延迟[OR=1.05,95%CI（0.38~2.90）,I2=0%,P=0.92]、24 h[SMD=0.49,95%CI（-0.59~1.57）,I2=83%,P=0.37]和42 h[SMD=0.03,95%CI（-0.40~0.47）,I2=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。

关键词: ABCB1, 基因多态性, 甲氨蝶呤, 急性淋巴细胞白血病, 安全性, 系统评价, Meta分析

Abstract: 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), I2=0%, P=0.002]. There was no association between ABCB1 C3435T genetic polymorphisms and mucositis[OR=1.44, 95% CI (0.94~2.19), I2=25%, P=0.09], gastrointestinal reaction[OR=0.91, 95% CI (0.54~1.54), I2=0%, P=0.74], myelosuppression [OR=1.24, 95%CI (0.42~3.67), I2=74%, P=0.69], renal insufficiency[OR=0.51, 95% CI (0.13~1.93), I2=0%, P=0.32], excretion delay [OR=1.05, 95% CI (0.38~2.90), I2=0%, P=0.92] , 24 h[SMD=0.49, 95% CI (-0.59~1.57), I2=83%, P=0.37] and 42h [SMD=0.03, 95% CI(-0.40~0.47), I2=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 .

Key words: ABCB1, genetic polymorphisms, methotrexate, acute lymphoblastic leukemia, safety, systematic review, Meta analysis

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