NUDT15基因突变与硫唑嘌呤骨髓抑制相关性的Meta分析  

The association between NUDT15 gene mutation and azathioprine myelosuppression:a meta-analysis

作　　者：谢宏钗 陈金通[1] 郑玮玮[1] 俞星[1] 林艺娟[1] 刘艺娟 范华[1] 王承党[1] Xie Hongchai;Chen Jintong;Zheng Weiwei;Yu Xing;Lin Yijuan;Liu Yijuan;Fan Hua;Wang Chengdang(Department of Gastroenterology,Institute of Digestive Diseases,The First Affiliated Hospital,Fujian Medical University,Fuzhou 350000,China)

机构地区：[1]福建医科大学附属第一医院消化内科福建医科大学消化系疾病研究室,福州350000

出　　处：《中华炎性肠病杂志（中英文）》2020年第4期322-327,共6页Chinese Journal of Inflammatory Bowel Diseases

基　　金：福建省卫计委创新课题基金(2018-CX-32);福建省卫计生青年课题科研基金(2017-1-53)。

摘　　要：目的:分析炎症性肠病(IBD)人群中,NUDT15基因多态性与硫唑嘌呤(AZA)导致骨髓抑制不良反应的相关性,为IBD临床治疗提供参考。方法:通过计算机检索中国知网、万方、维普数据库、PubMed、Cochrane图书馆和Web of Science,筛选NUDT15基因突变与AZA治疗IBD的随机对照试验文献,并对符合纳入标准的研究进行质量评价和资料提取,进行Meta分析。结果:纳入10篇文献,共3095例患者。Meta分析显示,亚洲IBD人群中NUDT15基因突变率明显高于TPMT基因突变率(21.5%比2.8%,OR=0.10,95%CI:0.07~0.15,P<0.001),差异具有统计学意义;NUDT15基因突变与AZA相关的白细胞减少具有显著相关性(OR=0.40,95%CI:0.34~0.47,P<0.001);NUDT15突变的IBD患者更易在应用AZA的早期出现白细胞减少(OR=2.69,95%CI:1.67~4.33,P<0.001);同时NUDT15基因纯合突变型(TT型)更易出现Ⅲ~Ⅳ级的骨髓抑制(OR=0.09,95%CI:0.04~0.18,P<0.001)。结论:亚洲IBD人群中,AZA引起的骨髓抑制与NUDT15基因突变具有显著相关性,较TPMT基因突变关系更为密切,并多发生于应用AZA的8周内。同时,NUDT15基因TT纯合突变会增加重度骨髓抑制的风险。Objective To analyze the association between NUDT15 gene polymorphism and adverse reactions induced by azathioprine(AZA)myelosuppression in patients with inflammatory bowel disease(IBD),and to provide reference for clinical treatment of IBD.Methods Literatures of randomized controlled trials of NUDT15 gene mutation and AZA in the treatment of IBD were searched with computer from China Knowledge Network,Wanfang database,VIP database,PubMed,Cochrane Library and Web of Science.The quality evaluation and data of studies meeting the inclusion criteria were screened and retrieved to perform meta analysis.Results Ten literatures were enrolled including 3095 patients.Meta analysis showed that the mutation rate of NUDT15 gene in Asian IBD population was significantly higher than that of TPMT gene(21.5%vs.2.8%,OR=0.10,95%CI:0.07-0.15,P<0.001)with significant difference.NUDT15 gene mutation was significantly associated with AZA-related leukopenia(OR=0.40,95%CI:0.34-0.47,P<0.001).IBD patients with NUDT15 mutation were more likely to develop leukopenia in the early stage of AZA application(OR=2.69,95%CI:1.67-4.33,P<0.001).Besides,homozygous mutants of NUDT15 gene(TT type)were more likely to have gradeⅢ-Ⅳbone marrow suppression(OR=0.09,95%CI:0.04-0.18,P<0.001).Conclusions In Asian IBD population,bone marrow suppression caused by AZA is significantly associated with NUDT15 gene mutation,which is more closely associated than TPMT gene mutation and usually occurs within 8 weeks of AZA application.At the same time,homozygous mutations of NUDT15 gene(TT)increase the risk of severe myelosuppression.

关 键 词：炎症性肠病 NUDT15 硫唑嘌呤 骨髓抑制 META分析 

分 类 号：R574[医药卫生—消化系统]