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
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篇名: 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
TITLE: Meta-analysis of the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram
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、theCochraneLibrary、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RevMan5.3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/SSvs.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/SSvs.LL:OR=0.92,95%CI(0.77,1.10),P>0.05;SSvs.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rs25531LA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HTTLPRLL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。
ABSTRACT: 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 9 836 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.
期刊: 2023年第34卷第14期
作者: 陈诗狄;赵金;刘芳;易湛苗
AUTHORS: CHEN Shidi,ZHAO Jin,LIU Fang,YI Zhanmiao
关键字: 西酞普兰;艾司西酞普兰;有效性;安全性;基因多态性;Meta分析
KEYWORDS: citalopram; escitalopram; efficacy; safety;
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