急性淋巴细胞白血病患儿的rs116855232基因多态性与巯嘌呤所致不良反应相关性  

Association Between Rs116855232 Gene Polymorphisms and Mercaptopurine-induced Adverse Reactions in Children with Acute Lymphoblastic Leukemia

作　　者：李惠英[1] 沈建玲 茹毅 涂彩霞 李云巍[1] 任丹阳[1] Li Huiying;Shen Jianling;Ru Yi;Tu Caixia;Li Yunwei;Ren Danyang(Department of Pharmacy,Kunming Children*s Hospital,Kunming 650228,China)

机构地区：[1]昆明市儿童医院药剂科,昆明650228

出　　处：《药物流行病学杂志》2021年第9期596-600,共5页Chinese Journal of Pharmacoepidemiology

基　　金：云南省昆明市科技计划项目(编号:2017-1-S16778);昆明市卫生科技人才培养项目(编号:2019-后备人选-32)。

摘　　要：目的:了解NUDT15 rs116855232基因多态性与急性淋巴细胞白血病(ALL)患儿巯嘌呤化疗后不良反应的相关性。方法:94例ALL患儿采用荧光染色原位杂交测序法检测NUDT15 rs116855232基因型,比较维持治疗阶段不同基因型患儿巯嘌呤所致不良反应发生情况。结果:维持治疗阶段,大部分患儿出现骨髓抑制、肝脏毒性和口腔黏膜/胃肠道反应等不良反应。与NUDT15 rs116855232 CC基因型ALL患儿相比,CT、TT基因型患儿发生白细胞减少、血红蛋白下降和血小板减少的比例更高(P<0.05)。而NUDT15 rs116855232不同基因型患儿发生中性粒细胞减少、肝脏毒性和口腔黏膜/胃肠道反应差异均无统计学意义(P>0.05)。结论:ALL患儿NUDT15 rs116855232基因多态性可能与巯嘌呤所致白细胞减少等骨髓抑制有关。ALL患儿可根据NUDT15 rs116855232基因检测结果调整巯嘌呤剂量,以减少骨髓抑制等不良反应的发生。Objective:To understand the correlation between the polymorphism of NUDT15 rs116855232 gene and adverse reactions after thiopurine chemotherapy in children with acute lymphoblastic leukemia(ALL).Methods:The genotypes NUDT15 rs116855232 were detected by fluorescence staining in situ hybridization sequencing in 94 children with all, and the incidence of adverse reactions caused by mercaptopucine in different genotypes was compared during maintenance treatment.Results:During the maintenance treatment period, most of the children had myelosuppression, hepatotoxicity and oral cavity mucous membrane/gastrointestinal reactions. Compared with ALL children with NUDT15 rs116855232 CC genotype, the proportion of leukopenia, hemoglobin reduction and thrombocytopenia was higher in children with CT and TT genotypes(P<0.05). There was no significant difference between NUDT15 rs116855232 genotypes and mercaptopurine induced neutropenia, liver toxicity and cavity mucous membrane/gastrointestinal reactions(P>0.05). Conclusion:The polymorphism of NUDT15 rs116855232 gene in all children may be related to mercutopurine-induced bone marrow suppression. According to the NUDT15 rs116855232 gene detection results, the dosage of mercutopurine can be adjusted in children with all to reduce the occurence of adverse reactions such as myelosuppression.

关 键 词：巯嘌呤 急性淋巴细胞白血病 儿童 NUDT15 rs116855232 基因多态性 药品不良反应 

分 类 号：R733.71[医药卫生—肿瘤]