男性精神分裂症患者服用氯氮平疗效与多巴胺D_1受体基因多态性的相关性研究

Study on Relationship between Dopamine D_1 Receptor Gene Polymorphisms and Clozapine Efficacy in Male Schizophrenic Patients

目的：探讨中国男性精神分裂症患者多巴胺D1受体基因多态性对服用氯氮平后血药浓度与疗效的影响。方法：46例男性精神分裂症患者单一服用氯氮平治疗6-8周,采用阳性与阴性症状量表（PANSS）评定氯氮平的疗效。测定氯氮平血药浓度,并通过测定基因序列检测多巴胺D1受体上rs265981、rs5326、rs4532、rs1799914、rs686、rs4867798等6个SNP位点的基因型和等位基因频率。结果：氯氮平总疗效有效组与无效组相比,rs265981基因型TT、TC、CC及等位基因T、C的分布差异有统计学意义（P=0.025;P=0.005）,rs686基因型CC、CT、TC及等位基因C、T的分布差异有统计学意义（P=0.044;P=0.010）。阴性症状有效组与无效组相比,rs4532基因型GG、GA、AA及等位基因G、A的分布差异有统计学意义（P=0.034;P=0.013）。结论：氯氮平治疗男性精神分裂症的总疗效个体差异可能与多巴胺D1受体基因rs265981、rs686有关,阴性症状疗效可能与rs4532有关。

Objective： To investigate the relationship between dopamine D1receptor（ DRD1） gene polymorphisms and clozapine efficacy in male schizophrenic patients. Methods： Totally 46 male schizophrenic patients were treated by clozapine for 6-8 weeks. The clinical response was determined by the Positive and Negative Symptom Scale（ PANSS）. DRD1 gene rs265981,rs5326,rs4532,rs1799914,rs686 and rs4867798 polymorphisms were detected by the gene sequencing,while plasma clozapine levels were monitored during the treatment. Results： The total clinical efficacy of clozapine response group and the non-response group was compared,the distribution of rs265981 genotype TT,TC and CC and allele T and C had statistically significant differences（ P = 0. 025; P = 0. 005）,and the distribution of rs686 genotype CC,CT and TC and allele C and T had statistically significant differences（ P = 0. 044; P =0. 010）. The negative symptom of the response group was compared with that of the non-response group,the distribution of rs4532 genotype GG,GA and AA and allele G and A had statistically significant differences（ P = 0. 034; P = 0. 013）. Conclusion： The polymorphisms of DRD1 gene rs265981 and rs686 may have influence on the clinical efficacy of clozapine,and rs4532 may have influence on the negative symptom.