CYP2D6*10基因多态性对喹硫平血药浓度和临床疗效的影响

Effect of CYP2D6*10 Genetic Polymorphism on Blood Concentration and Clinical Efficacy of Quetiapine

关键词:  精神分裂症  喹硫平  CYP2D6*10基因多态性  血药浓度  临床疗效

Key words:  schizophrenia  quetiapine  CYP2D6*10 genetic polymorphism  blood concentration  clinical efficacy

摘要:

目的 探讨细胞色素P450 2D6（CYP2D6）基因多态性对精神分裂症患者喹硫平血药浓度和临床疗效的影响，为喹硫平的个体化给药提供参考。方法 选取符合诊断标准的精神分裂症住院患者98例，接受喹硫平单一治疗，剂量范围为100~750 mg·d^-1，观察疗程为4周。采用多重高温连接酶检测反应技术检测CYP2D6*10基因多态性，采用UPLC-MS/MS测定喹硫平血药浓度，以治疗前后阳性和阴性症状量表（PANSS）评分变化评价临床疗效，并比较不同基因型之间喹硫平血药浓度和临床疗效的差异。结果 TT型患者喹硫平血药浓度明显高于CC型和CT型患者（P<0.05），且喹硫平血药浓度与CYP2D6*10基因型存在相关关系（r=0.558，P<0.001）；TT型患者治疗有效率最高，CT型次之，CC型最低，差异有统计学意义（P<0.05）；治疗后TT型患者PANSS量表总减分值、阳性症状减分值和阴性症状减分值均明显高于CC型患者（P<0.05）。结论 CYP2D6*10基因多态性可影响喹硫平血药浓度和临床疗效，CC型患者用喹硫平治疗时血药浓度偏低且疗效较差，临床医生用药时应予以关注。

Abstract:

OBJECTIVE To investigate the effect of cytochrome P450 2D6(CYP2D6) genetic polymorphism on blood concentration and clinical efficacy of quetiapine in schizophrenia patients, and to provide evidence for the individualized administration of quetiapine. METHODS A total of 98 patients with schizophrenia were selected and treated with quetiapine alone at a dose ranging from 100 to 750 mg·d^-1 for 4 weeks. The genetic polymorphism of CYP2D6*10 was detected by improved multiple ligase detection reaction. The blood concentration of quetiapine was determined by UPLC-MS/MS. Positive and negative syndrome scale(PANSS) questionnaire were used to estimate the response to quetiapine treatment. Then the differences in blood concentration and clinical efficacy of quetiapine among different genotypes were compared. RESULTS The blood concentration of quetiapine in type of TT was significantly higher than that in types of CC and CT(P<0.05). The blood concentration of quetiapine was correlated with CYP2D6*10 genotype(r=0.558, P<0.001). TT type patients had the highest treatment efficiency, followed by CT type and CC type, and the difference was statistically significant(P<0.05). The reductions of PANSS total score, positive symptom score and negative symptom score in TT type patients were significantly higher than that in type of CC after treatment(P<0.05). CONCLUSION CYP2D6*10 genetic polymorphism can affect the blood concentration and clinical efficacy of quetiapine. Patients with CC type have low blood concentration of quetiapine and poor clinical efficacy, so clinicians shall pay appropriate attention to it.