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·循证药学·
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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1*
陈诗狄 ,赵 金 ,刘 芳 ,易湛苗 (1.北京市海淀医院药学部,北京 100080;2.北京大学第三医院药剂
科,北京 100191)
中图分类号 R971+.4;R749.05 文献标志码 A 文章编号 1001-0408(2023)14-1748-07
DOI 10.6039/j.issn.1001-0408.2023.14.17
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9 836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。
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
Meta-analysis of the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram
CHEN Shidi ,ZHAO Jin ,LIU Fang ,YI Zhanmiao(1. Dept. of Pharmacy, Beijing Haidian Hospital, Beijing
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100080,China;2. Dept. of Pharmacy, Peking University Third Hospital, Beijing 100191, China)
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/
Δ 基金项目 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) *3 allele is significantly associated with higher response rate
*第一作者 主管药师,硕士。研究方向:临床药学、循证药学。电 and reduced tolerability.
话:010-82693357。E-mail:shidi_chen@163.com KEYWORDS citalopram; escitalopram; efficacy; safety;
# 通信作者 副主任药师,副教授,硕士生导师,博士。研究方向: gene polymorphism; meta-analysis
循证药学、临床药物治疗评价、药物经济学。电话:010-82265740。E-
mail:yzm@bjmu.edu.cn
· 1748 · China Pharmacy 2023 Vol. 34 No. 14 中国药房 2023年第34卷第14期