CYP1A2基因多态性对抗精神病药物血药浓度影响的Meta分析
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篇名: CYP1A2基因多态性对抗精神病药物血药浓度影响的Meta分析
TITLE: Effects of CYP1A2 Gene Polymorphisms on Blood Concentrations of Antipsychotic Drugs :A Meta-analysis
摘要: 目的:系统评价CYP1A2基因多态性对抗精神病药物(氟哌啶醇、氯氮平、奥氮平)血药浓度的影响,为临床用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、中国生物医学文献数据库、中国知网和万方数据等,检索时限均为建库起至2019年11月。收集CYP1A2基因多态性对抗精神病药物(氟哌啶醇、氯氮平、奥氮平)血药浓度影响的横断面研究。筛选文献、提取资料并采用Q-Genie工具对纳入文献质量进行评价后,采用RevMan5.3软件进行Meta分析。结果:共纳入11篇横断面研究,共计914例患者。其中,2项研究为氟哌啶醇,5项研究为氯氮平,4项研究为奥氮平。Meta分析结果显示,氟哌啶醇血药浓度方面,CYP1A2(-2964G>A)G/G型与G/A+A/A型[SMD=-0.22,95%CI(-0.66,0.23),P=0.35]比较,差异无统计学意义。氯氮平血药浓度方面,CYP1A2(-163C>A)A/C型显著低于C/C型[SMD=0.31,95%CI(0.01,0.62),P=0.04];而A/A型与C/C型[SMD=0.09,95%CI(-0.21,0.40),P=0.56]、A/A型与A/C型[SMD=-0.22,95%CI(-0.55,0.10),P=0.18]以及CYP1A2(-2467delT)delT/delT型与T/T型[SMD=-0.11,95%CI(-0.75,0.52),P=0.72]、delT/T型与T/T型[SMD=0.01,95%CI(-0.33,0.34),P=0.97]、delT/delT型与delT/T型[SMD=-0.15,95%CI(-0.80,0.15),P=0.66]比较,差异均无统计学意义。奥氮平血药浓度方面,CYP1A2(-163C>A)A/A型显著低于A/C型[SMD=-0.31,95%CI(-0.55,-0.08),P=0.009];而A/A型与C/C型[SMD=-0.20,95%CI(-0.61,0.21),P=0.34]、A/C型与C/C型[SMD=0.06,95%CI(-0.35,0.47),P=0.77]以及CYP1A2(-2467delT)delT/T型与T/T型[SMD=0.28,95%CI(-0.15,0.71),P=0.20]比较,差异均无统计学意义。结论:CYP1A2(-163C>A)A/C型与氯氮平血药浓度降低有关,A/A型与奥氮平血药浓度降低有关;检测CYP1A2(-163C>A)基因多态性对精神障碍患者的个体化用药具有指导意义。
ABSTRACT: OBJECTIVE:To systematically evaluate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs (haloperidol,clozapine,olanzapine),and to provide evidence-based reference for the clinical drug use . METHODS:Retrieved from Cochrane Library ,PubMed,Embase,CBM,CNKI and Wanfang data ,during the inception to Nov. 2019,cross-sectional study was conducted to investigate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs (haloperidol,clozapine,olanzapine)were collected. After screening the literature ,extracting the data and quality evaluation with Q-Genie tool ,Meta-analysis was performed by using Rev Man 5.3 software. RESULTS :A total of 11 cross-sectional studies were included ,with a total of 914 patients. Of these ,haloperidol was used in 2 studies,clozapine was used in 5 studies,and olanzapine was used in 4 studies. Meta-analysis showed that there was no statistically significant difference in the blood concentration of haloperidol between CYP1A2(-2964G>A)G/G type and G/A+A/A type [SMD =-0.22,95%CI(-0.66, 0.23),P=0.35]. The blood concentration of clozapine in CYP1A2(-163C>A)A/C type was significantly lower than C/C type [SMD =0.31,95%CI(0.01,0.62),P=0.04];there was no statistical significance in blood concentration of clozapine between A/A type and C/C type [SMD =0.09,95%CI(-0.21,0.40),P=0.56],between A/A type and A/C type [SMD =-0.22,95%CI(-0.55, 0.10),P=0.18],between CYP1A2(-2467delT)delT/delT type and T/T type [SMD =-0.11,95%CI(-0.75,0.52),P=0.72], between delT/T type and T/T type [SMD =0.01,95%CI(-0.33,0.34),P=0.97],between delT/delT type and delT/T type [SMD = -0.15,95%CI(-0.80,0.05),P=0.66]. The blood concentration of olanzapine in CYP1A2(-163C>A)A/A type was signifi- cantly lower than A/C type [SMD =-0.31,95%CI(-0.55, - 0.08),P=0.009];there was no statistically significant difference in the blood concentration of olanzapine between A/A liukefeng-num.1@163.com type and C/C type [SMD =-0.20,95%CI(-0.61,0.21),P= 0.34],between A/C type and C/C type [SMD =0.06,95%CI E-mail:hnmuzj@163.com (-0.35,0.47),P=0.77],between CYP1A2(-2467delT)delT/T type and T/T type [SMD =0.28,95%CI(-0.15,0.71),P=0.20]. CONCLUSIONS:CYP1A2(-163C>A)A/C type is related to the reduction of clozapine blood concentration ,and A/A type is related to the reduction of olanzapine blood concentration. CYP1A2 (-163C>A)gene polymorphism is significance for guiding individualized medication of schizophrenia patients.
期刊: 2020年第31卷第14期
作者: 刘克锋,乔高星,张旭锋,朱琦玥,刘宇,赵杰
AUTHORS: LIU Kefeng ,QIAO Gaoxing ,ZHANG Xufeng ,ZHU Qiyue,LIU Yu,ZHAO Jie
关键字: CYP1A2;基因多态性;抗精神病药物;血药浓度;Meta分析
KEYWORDS: CYP1A2;Gene polymorphism ;Antipsychotic drugs ;Blood concentration ;Meta-analysis
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