细胞色素P450 2D6/C188T酶基因多态性与阿立哌唑治疗效应的关系

Association study of cytochrome P450 2D6/C188T gene polymorphism and therapeutic response to aripiprazole in Chinese subjects with schizophrenia

目的研究精神分裂症患者细胞色素P450 2D6酶(CYP2D6)exonⅠC/T188基因多态性与阿立哌唑治疗效应的关系。方法采用阳性和阴性症状量表(PANSS),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92例精神分裂症患者,分别在阿立哌唑治疗前及治疗第1、2、4、6、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CYP2D6 exon Ⅰ C/T188基因多态性进行检测。根据其基因型将患者分为三组(C/C组30例、C/T组38例、T/T组24例),采用治疗前后PANSS减分率≥30%为标准,将92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。结果从阿立哌唑治疗后第6周末开始,三组之间PANSS评分的差异有显著性(P<0.01);两两比较发现,C/C组PANSS分低于T/T组(P<0.01);CYP2D6 exonⅠC/T188多态性基因型频率和等位基因频率,阿立哌唑治疗有效组与无效组之间的差异有显著性。但未发现基因型与阿立哌唑药物副反应有关。结论中国人群精神分裂症CYP2D6 exonⅠC/T188多态性可能是影响阿立哌唑临床疗效的遗传易感因素。

Objective To investigate whether cytochrome P450 2D6/C188T gene polymorphism （CYP2D6/ C188T） is associated with therapeutic response to aripiprazole in Chinese patients with schizophrenia. Methods Ninety-two cases with schizophrenia were assessed with the Positive and Negative Syndrome Scale（ PANSS）, Treatment Emergent Symptoms Scale（TESS） and Rating Scale for Extrapyramidal Side Effects（RSESE）. They were used at baseline and at 1,2,4,6,8 weekend during the 8-week aripiprazole treatment. CYP2D6 gene exon Ⅰ C/T188 polymorphism was 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%. Results From the sixth weekend of aripiprazole 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 ）. Distributions of the genotype frequencies and allele frequencies were different significantly between the treatment responder and non-responder group. But there was no association between genotypes and treatment side effects of aripiprazole. Conclusion The CYP2D6 gene exon ⅠC/T188 polymorphism is possible a genetic susceptibility factor for therapeutic response to aripiprazole in Chinese patients with schizophrenia.