Effects of CYP1A2 Gene Polymorphisms on Blood Concentrations of Antipsychotic Drugs ：A Meta-analysis / 中国药房

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.