精神分裂症患者CYP2D6基因多态性与利培酮血药浓度及临床疗效关系探究  

Relationship between CYP2D6 Gene Polymorphism and Risperidone Plasma Concentration with Clinical Efficacy in Patients with Schizophrenia

作　　者：王皓 徐红林 钱博文 黄永祥 WANG Hao;XU Hong-lin;QIAN Bo-wen;HUANG Yong-xiang(Department of Psychiatry,the Second Hospital of WISCO,Wuhan 430080,China)

机构地区：[1]武钢第二职工医院精神科,武汉430080

出　　处：《解放军医药杂志》2020年第8期44-48,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：湖北省卫生健康委员会科研项目(WJ2019F036)。

摘　　要：目的探索精神分裂症(SCH)患者细胞色素P450家族2D6(CYP2D6)基因多态性与利培酮(RISP)血药浓度及临床疗效之间的关系。方法回顾性分析2019年1月—8月我院收治的196例SCH患者的临床资料,将其分为正常功能组(携带CYP2D6*1或*2)40例、低功能1组(携带一个CYP2D6*10)89例及低功能2组(携带2个CYP2D6*10)67例。3组均口服RISP,治疗4周后分析血RISP和9羟基利培酮(9-OH-RISP)浓度及CYP2D6基因多态性;治疗8周后评估3组临床疗效,计算简明精神病量表(BPRS)减分率和不良反应症状量表(TESS)评分。分析CYP2D6基因多态性与9-OH-RISP/RISP比值、BPRS减分率和TESS评分之间的相关性。结果SCH患者CYP2D6*1等位基因频率为29.59%,CYP2D6*2等位基因频率为13.52%,CYP2D6*10等位基因频率为56.89%。正常功能组和低功能1组RISP血药浓度、BPRS减分率和TESS评分显著低于低功能2组,9-OH-RISP和9-OH-RISP/RISP比值显著高于低功能2组(P<0.05)。携带CYP2D6*10与9-OH-RISP/RISP比值呈明显负相关(r=-0.378,P<0.001),与BPRS减分率和TESS评分呈明显正相关(r=0.242、0.284,P<0.05)。结论CYP2D6基因多态性与RISP在体内的代谢速率及其治疗的临床疗效有关。Objective To explore relationship between gene polymorphism of cytochrome P450 family 2 subfamily D member 6(CYP2D6)and Risperidone(RISP)plasma concentration,clinical efficacy of patients with schizophrenia(SCH).Methods A retrospective analysis was performed on 196 SCH patients who were admitted to our hospital from January to August 2019.They were divided into normal function group(n=40,carrying CYP2D6*1 or*2),low function 1 group(n=89,carrying a CYP2D6*10)and low function 2 group(n=67,carrying 2 CYP2D6*10).All patients included were treated with oral RISP.At 4 weeks after treatment,concentrations of blood RISP and 9 hydroxykirisperidone(9-OH-RISP)were analyzed and CYP2D6 gene polymorphism was detected.At 8 weeks after treatment,clinical efficacy was evaluated,and reduction rate of brief psychiatric rating scale(BPRS)and score of treatment emergent symptom scale(TESS)were calculated.The correlation between CYP2D6 gene polymorphism and 9-OH-RISP/RISP,BPRS reduction rate,TESS score was analyzed.Results The allele frequencies of CYP2D6*1,CYP2D6*2 and CYP2D6*10 in SCH patients were 29.59%,13.52%and 56.89%,respectively.RISP plasma concentration,reduction rate of BPRS and TESS score in normal function group and low function 1 group were significantly lower than those in low function 2 group,while 9-OH-RISP and 9-OH-RISP/RISP were significantly higher than those in low function 2 group(P<0.05).CYP2D6*10 was significantly and negatively correlated with 9-OH-RISP/RISP(r=-0.378,P<0.001),while significantly and positively correlated with reduction rate of BPRS and TESS score(r=0.242 and 0.284,P<0.05).Conclusion CYP2D6 gene polymorphism is related to metabolic rate of RISP in vivo and its clinical efficacy.

关 键 词：精神分裂症 细胞色素P450家族2D6 利培酮 血药浓度 基因 代谢清除率 

分 类 号：R749.3[医药卫生—神经病学与精神病学]