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基因多态性对西酞普兰/艾司西酞普兰有效性与安全性影响的Meta分析

Meta-analysis of the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram
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摘要 目的评价基因多态性对西酞普兰/艾司西酞普兰有效性与安全性的影响,为临床精准用药提供循证参考。方法计算机检索PubMed、Embase、the Cochrane Library、中国知网、万方数据、中国生物医学文献服务系统,收集基因多态性与西酞普兰/艾司西酞普兰有效性、安全性相关的临床研究,筛选文献,提取资料并采用纽卡斯尔-渥太华量表评价文献质量后,采用RevMan 5.3软件进行Meta分析。结果共纳入35篇文献,均为队列研究,共计9836例患者。Meta分析结果显示,SLC6A4基因5-羟色胺转运体启动子(HTTLPR)LL基因型与西酞普兰/艾司西酞普兰有效率升高[LS/SS vs.LL:OR=0.47,95%CI(0.22,0.98),P=0.05]相关;亚组分析结果显示,携带LL基因的白种人或使用艾司西酞普兰的有效率更高。SLC6A4基因HTTLPR基因型与治愈率[LS/SS vs.LL:OR=0.92,95%CI(0.77,1.10),P>0.05;SS vs.LL/LS:OR=0.73,95%CI(0.45,1.19),P>0.05]无显著相关性。HTTLPR基因多态性与总体不良反应发生率无显著相关性,但rs25531 LA的高表达与不良反应发生率降低显著相关(P<0.05)。CYP2C19*2/*3等位基因与西酞普兰/艾司西酞普兰体内代谢减慢、有效率升高及不良反应发生率升高均显著相关。结论HTTLPR LL基因型与西酞普兰/艾司西酞普兰有效率升高相关,与安全性无显著相关性;CYP2C19*2/*3等位基因与有效率更高、耐受性降低均显著相关。 OBJECTIVE To evaluate the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram,and to provide evidence-based reference for precision medication.METHODS Retrieved from PubMed,Embase,the Cochrane Library,CNKI,Wanfang data and SinoMed,clinical studies about the association of gene polymorphism with efficacy and safety of citalopram/escitalopram were collected.Meta-analysis was performed with RevMan 5.3 software after literature screening,data extraction and quality evaluation based on Newcastle-Ottawa scale.RESULTS Totally 35 pieces of literature were included,all of which were cohort studies,with a total of 9836 patients.Meta-analysis showed that the SLC6A4 gene 5-serotonin transporter linked polymorphic region(HTTLPR)LL genotype was associated with high response rate of citalopram/escitalopram[LS/SS vs.LL:OR=0.47,95%CI(0.22,0.98),P=0.05];results of subgroup analysis suggested a higher correlation in white people with LL genotype and escitalopram;there was no significant correlation of HTTLPR genotype with remission rate[LS/SS vs.LL:OR=0.92,95%CI(0.77,1.10),P>0.05;SS vs.LL/LS:OR=0.73,95%CI(0.45,1.19),P>0.05]or overall incidence of ADR in patients with gene SLC6A4;but high expression of rs25531 LA was significantly associated with reduced incidence of ADR(P<0.05).CYP2C19*2/*3 allele was significantly associated with slowed metabolism,higher response rate and increased incidence of ADR.CONCLUSIONS HTTLPR LL genotype is associated with the increased response rate of citalopram/escitalopram,but no significant correlation with safety is found,while CYP2C19*2/*3 allele is significantly associated with higher response rate and reduced tolerability.
作者 陈诗狄 赵金 刘芳 易湛苗 CHEN Shidi;ZHAO Jin;LIU Fang;YI Zhanmiao(Dept.of Pharmacy,Beijing Haidian Hospital,Beijing100080,China;Dept.of Pharmacy,Peking University Third Hospital,Beijing 100191,China)
出处 《中国药房》 CAS 北大核心 2023年第14期1748-1754,共7页 China Pharmacy
基金 国家自然科学基金资助项目(No.72104003) 国家重点研发计划项目(No.2020YFC2008305)。
关键词 西酞普兰 艾司西酞普兰 有效性 安全性 基因多态性 META分析 citalopram escitalopram efficacy safety gene polymorphism meta-analysis
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