精神分裂症患者细胞色素P4502D6酶基因多态性与利培酮治疗效应的关系

Association study of cytochrome P450 2D6 gene polymorphism and therapeutic response to risperidone in Chinese subjects with schizophrenia

目的 研究精神分裂症患者细胞色素P4 5 0 2D6酶 (CYP2D6 )多态性是否与利培酮治疗效应有关。方法 采用阳性和阴性症状量表 (PANSS)、大体评定量表 (GAS)、治疗时需处理的副反应量表 (TESS)以及锥体外系副反应量表 (RSESE)对 5 2例精神分裂症 [PANSS基线分 (10 5 5 9± 17 30 )分 ;GAS基线分 (31 75± 3 32 )分 ]患者 ,分别在利培酮治疗前及治疗 [(5± 3)mg/d]第 1～ 8周末各进行一次药物反应评定 ,采用聚合酶链反应技术对CYP2D6exonⅠC/T188和CYP2D6G/A1934两个多态性位点进行检测。根据CYP2D6exonIC/T188基因型将患者分为三组 (C/C组 13例 ,C/T组 2 0例 ,T/T组19例 ) ;采用治疗前后PANSS 30 %减分率为标准 ,将 5 2例患者分为治疗有效组和治疗无效组 ,比较组间药物治疗效应的差异。结果 从利培酮治疗后第 5周末开始 ,三组之间PANSS评分的差异有显著性 (P <0 0 1) ;两两比较发现 ,C/C组PANSS分低于T/T组 (P <0 0 1) ;三组之间GAS评分的差异从第6周开始出现显著性 (P <0 0 1) ,其中C/C组GAS分明显高于T/T组 (P <0 0 1)。多因素方差分析显示 ,三组的PANSS总分 (F =2 6 4 ,P <0 0 1)及GAS评分 (F =1 85 ,P <0 0 5 )差异有非常显著性 ;CYP2D6exonⅠC/T188多态性基因型频率 (χ2 =6 5 6 ,P <0

Objective To investigate whether cytochrome P450 2D6 gene polymorphism (CYP2D6) was associated with therapeutic response to risperidone in Chinese subjects with schizophrenia Methods Fifty two cases with schizophrenia were assessed with the Positive and Negative Syndrome Scale (PANSS), General Assessment Scales (GAS), Treatment Emergent Symptoms Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used at baseline and at each weekend during the 8 week risperidone treatment CYP2D6 gene exon Ⅰ C/T188 and CYP2D6 G/A1934 polymorphisms were detected with polymerase chain reaction The patients were divided into three groups according to the CYP2D6 exon I C/T188 genotypes (C/C, C/T and T/T group) The cases were also categorized into treatment responder or non responder group according to whether the reduction on PANSS score was more than 30% or not Results From the fifth weekend of risperidone therapy, the PANSS scores in the three genotype groups were different significantly ( P <0 01), with the lower score in group C/C than that in group T/T ( P <0 01) Difference on the GAS score among the three groups occurred at the end of sixth week ( P <0 01), with higher score in group C/C than that in group T/T ( P <0 01) Multiple analysis of variance showed significant difference on PANSS ( F =2 64, P <0 01) and GAS score ( F =1 85, P <0 05) among these three groups Distributions of the genotype frequencies (χ 2=6 56, P <0 05) and allele frequencies (χ 2=5 03, P <0 05; RR : 2 54, 95% CI : 1 40-8 32) were different significantly between the treatment responder and non responder group The CYP2D6 G/A1934 polymorphism was not found in this sample Conclusions The CYP2D6 gene exon Ⅰ C/T188 polymorphism is possible a genetic susceptibility factor for therapeutic response to risperidone in Chinese subjects with schizophrenia