精神分裂症患者CYP2D6*10基因多态性与血清利培酮浓度的量化关系研究  

Quantitative relationship between CYP2D6*10 gene polymorphism and serum risperidone concentration in patients with schizophrenia

作　　者：陈洁 宋明芬[2] 闫盼 王姝琪 王晟东[2] 王泽民[3] 王玉文[3] 施剑飞[4] CHEN Jie;SONG Mingfen;YAN Pan;WANG Shuqi;WANG Shengdong;WANG Zemin;WANG Yuwen;SHI Jianfei(The 4th Clinical College,Zhejiang Chinese Medical University,Hangzhou 310053,China;不详)

机构地区：[1]浙江中医药大学第四临床医学院,杭州310053 [2]杭州市第七人民医院分子生物学实验室 [3]杭州市第七人民医院药剂科 [4]杭州市第七人民医院精神科

出　　处：《浙江医学》2023年第1期48-51,57,共5页Zhejiang Medical Journal

基　　金：浙江省医药卫生科技计划项目(2020KY744、2020KY2222);浙江省科技计划项目(2015C03054);浙江省公益技术应用研究项目(LGF22H090014);杭州市医药卫生科技计划项目(ZD20200078)。

摘　　要：目的探讨精神分裂症患者细胞色素P450(CYP)2D6*10基因多态性对血清利培酮浓度的影响及其量化关系。方法选取2019年5月至2022年5月杭州市第七人民医院收治住院的接受利培酮单一治疗的精神分裂症患者197例为研究对象,采用随机数字表法分为血清利培酮浓度预测模型的预测组99例和验证组98例。采用荧光PCR法检测CYP2D6*10基因多态性,采用超高效液相色谱-串联质谱法检测治疗4周时血清利培酮浓度,运用曲线估计对CYP2D6*10基因多态性与血清利培酮浓度进行量化关系分析。结果药物剂量、CYP2D6*10代谢酶基因型与血清利培酮浓度均显著相关(均P<0.01)。不同CYP2D6*10基因型的血清利培酮浓度与药物剂量之间存在幂函数曲线拟合(r=0.84,P<0.01)。模型验证中,预测利培酮浓度和实际利培酮浓度之间高度相关(r=0.81,P<0.01)。结论不同CYP2D6*10基因型的血清利培酮浓度与药物剂量之间存在幂函数的量化关系。Objective To explore the correlation of cytochrome P450(CYP)2D6*10 gene polymorphism with serum risperidone concentration in schizophrenic patients.Methods A total of 197 schizophrenic patients treated with risperidone monotherapy in Hangzhou Seventh People’s Hospital from May 2019 to May 2022 were recruited.The patients were randomly divided into a training group(99 cases)and a validation group(98 cases)for establishing a drug concentration prediction model.The polymorphism of CYP2D6*10 gene was detected by fluorescent PCR method.The serum concentration of risperidone was determined by ultra performance liquid chromatography-tandem mass spectrometry at week 4 of treatment.Curve estimation was used to quantify the relationship between CYP2D6*10 gene polymorphism and serum risperidone concentration.Results Drug dose and CYP2D6*10 genotypes were significantly correlated with serum risperidone concentration(all P<0.01).A power function curve fitting was obtained between the serum risperidone concentration and dosage for different CYP2D6*10 genotypes(r=0.84,P<0.01).In model validation,the predicted drug concentrations based on the power functions were highly the actual drug concentrations(r=0.81,P<0.01).Conclusion Serum risperidone concentration can be described as power functions of drug doses based on CYP2D6*10 genotypes.

关 键 词：CYP2D6*10基因多态性 血清利培酮浓度 精神分裂症 

分 类 号：R749.3[医药卫生—神经病学与精神病学]