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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
                         Δ

                           1
                                             2 #
                                   1, 2
                 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
                                1
                     1
                                                         2
                                          1, 2
          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
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