拉帕替尼引起胃肠道不良反应与相关基因的关联性研究  

Study of Correlation Between Lapatinib-induced Gastrointestinal Reactions and Related Genes

作　　者：陈婕[1] 储文功[1] 潘建玲[1] 

机构地区：[1]第二军医大学药学院药事管理教研室,上海200433

出　　处：《药物流行病学杂志》2016年第6期359-362,共4页Chinese Journal of Pharmacoepidemiology

摘　　要：目的:通过生物信息学方法对拉帕替尼引起胃肠道不良反应和基因的关联进行研究。方法:使用报告比值比(ROR)和条件概率两种计算方法,从毒理基因组学数据库(CTD)和收录了上市药品不良反应信息的副反应资源库(SIDER)收集目前上市小分子靶向抗肿瘤药的药物-基因相互作用信息和不良反应数据进行整合处理,计算拉帕替尼关联的16个基因与4项胃肠道不良反应的关联性。结果:拉帕替尼引起胃肠道不良反应相关的64对基因-不良反应配对中,ROR检出了18对信号,与条件概率值前30%(19对)的重合率为83.3%(15对),高关联的几个基因为EGFR、Erb B3、FSHβ和LHB。结论:拉帕替尼会引起基因EGFR和FSHβ表达异常,与胃肠道不良反应的关联性仍需进一步验证。生物信息学方法可以有效的筛选出高关联的基因-不良反应配对,为进一步分子生物学和流行病学研究提供数据基础和理论参考。Objective：To evaluate the correlation between adverse drug reactions and genes of lapatinib by bioinformatics methods. Methods： The drug-gene interaction and ADR data of in-market small-molecule targeted anti-tumor drugs are collected from CTD and SIDER databases and integrated. Two algorithms, ROR（reporting odds ratio） and conditional probability are applied to evaluate the association of 16 lapatinib-associated genes and 4 gastrointestinal reactions. Results：From all 64 lapatiuib-associated gene-ADR pairs, ROR detected 18 pairs which has an overlap of 83.3% （15 pairs） with top 30% probability value. The result suggested that EGFR, ErbB3, FSH[3 and LHB were relatively highly associated with lapatinib-induced gastrointestinal reactions. Conclusion： Lapatinib decreased the activity of EGFR and FSHβ, but further study was needed to determine the association between gene abnormal expression and gastrointestinal reactions. Bioinformatics methods could be used to screen out potential gene-ADR pairs with strong correlation, which served as a basis for further molecular biology and epidemiology research.

关 键 词：拉帕替尼 药品不良反应 基因 生物信息学 

分 类 号：R979.1[医药卫生—药品]