CYP1A2基因多态性对抗精神病药物血药浓度影响的Meta分析

Effects of CYP1A2 Gene Polymorphisms on Blood Concentrations of Antipsychotic Drugs:A Meta-analysis

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Rev Man 5.3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。

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 significantly 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 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(-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 tothe 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.