NUDT15基因多态性与巯嘌呤类药物所致白细胞减少相关性的Meta分析  

Association between NUDT15 gene polymorphism and thiopurine-induced leukopenia:a Meta-analysis

作　　者：李剑钦 杨星辰[1] 陈连云 黄苏莉 LI Jianqin;YANG Xingchen;CHEN Lianyun;HUANG Suli(Department of Pharmacy,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Department of Pharmacy,Shanghai Yangpu Mental Health Center,Shanghai 200093,China)

机构地区：[1]上海中医药大学附属龙华医院药学部,上海200032 [2]上海市杨浦区精神卫生中心药剂科,上海200093

出　　处：《数理医药学杂志》2024年第2期119-127,共9页Journal of Mathematical Medicine

基　　金：龙华医院第二批药剂人才培养计划项目(RC-2020-03-01)。

摘　　要：目的系统评价NUDT15基因多态性与巯嘌呤类药物所致白细胞减少的相关性。方法计算机检索中国知网、万方、维普、中国生物医学文献、PubMed、Embase数据库获取相关文献,检索时限从建库至2023年6月。采用纽卡斯尔-渥太华量表(Newcastle-Ottawa Quality Assessment Scale,NOS)对纳入文献进行质量评价,采用Stata 14.0软件进行Meta分析。结果最终纳入17篇文献,共4057例患者,其中1017例患者使用巯嘌呤类药物后产生不同程度的白细胞减少或中性粒细胞减少。Meta分析结果显示,在NUDT15基因多态性下,各分组整体效应均具有统计学意义(P<0.001):用药8周内所致白细胞减少情况中,等位基因模型[OR=0.15,95%CI(0.10,0.22),P<0.001]、显性基因模型[OR=0.13,95%CI(0.08,0.20),P<0.001]、杂合基因模型[OR=0.04,95%CI(0.01,0.19),P<0.001]与白细胞减少具有显著相关性;用药超过8周所致白细胞减少情况中,等位基因模型[OR=0.18,95%CI(0.11,0.30),P<0.001]、显性基因模型[OR=0.17,95%CI(0.09,0.31),P<0.001]、杂合基因模型[OR=0.05,95%CI(0.02,0.15),P<0.001]与白细胞减少具有显著相关性;3~4级严重白细胞减少情况中,显性基因模型[OR=0.09,95%CI(0.05,0.15),P<0.001]与白细胞减少具有显著相关性。结论NUDT15基因多态性与巯嘌呤类药物所致白细胞减少具有相关性。Objective To systematically evaluate the association of NUDT15 gene polymorphism with thiopurine-induced leukopenia.Methods Relevant articles were searched electronically from CNKI,WanFang Data,VIP,CBM,PubMed and Embase from inception of the databases to June 2023.The quality of the included articles was evaluated using the Newcastle-Ottawa Quality Assessment Scale(NOS),a Meta-analysis was conducted by Stata https://slyyx.whuznhmedj.com/14.0 software.Results Seventeen articles involving 4057 patients were included.Among them,1017 patients developed leukopenia or neutropenia in varying degrees after using thiopurine drugs.Results of Meta-analysis showed that the overall effects of each group were statistically significant(P<0.001)under the NUDT15 gene polymorphism:for the leukopenia caused by medication within 8 weeks,the allele model[OR=0.15,95%CI(0.10,0.22),P<0.001],the dominant gene model[OR=0.13,95%CI(0.08,0.20),P<0.001],and the heterozygous gene model[OR=0.04,95%CI(0.01,0.19),P<0.001]were statistically associated with leukopenia;for the leukopenia after 8 weeks,the allele model[OR=0.18,95%CI(0.11,0.30),P<0.001],the dominant gene model[OR=0.17,95%CI(0.09,0.31),P<0.001],the heterozygous gene model[OR=0.05,95%CI(0.02,0.15),P<0.001]were statistically associated with leukopenia;for the grade 3 to 4 severe leukopenia,the dominant gene model[OR=0.09,95%CI(0.05,0.15),P<0.001]was statistically associated with leukopenia.Conclusion The polymorphism of NUDT15 gene was associated with leukopenia induced by thiopurines.

关 键 词：NUDT15 巯嘌呤 白细胞减少 基因多态性 META分析 

分 类 号：R557.1[医药卫生—血液循环系统疾病]