多巴胺D_3受体基因多态性与精神分裂症初发期患者抗精神病药疗效关系的研究

Association of dopamine D_3 receptor gene functional polymorphism with response to antipsychotics in first-episode schizophrenic patients

目的 探讨多巴胺D3 受体 (DRD3)基因多态性与精神分裂症初发期患者精神症状严重度和抗精神病药疗效是否相关。方法 对 10 9例精神分裂症初发期患者分别进行利培酮治疗 [4 3例 ,3～ 5mg/d ,平均 ( 4 0± 0 5 )mg/d]和氯丙嗪治疗 [6 6例 ,15 0～ 6 0 0mg/d ,平均 ( 339± 87)mg/d],疗程 10周。采用聚合酶链反应 限制性片段长度多态性技术检测其中 10 8例患者 (男 5 2例 ,女 5 6例 )DRD3基因ser9gly多态性。采用阳性和阴性症状量表 (PANSS)评定患者治疗前和治疗第 10周末的精神症状 ,并分析基因型及其他临床指标与PANSS分值和减分率的关系。结果 DRD3ser9gly基因型在各患者组分布频率均符合Hardy Weinberg定律 (P >0 0 5 ) ;基因型在治疗显效和未显著进步组分布频率的差异有显著性 ( χ2 =6 4 4 ,ν=2 ,P <0 0 5 ) ;各基因型亚组临床指标的差异均无显著性 (均P >0 0 5 ) ;基因型与患者治疗前PANSS总分及治疗第 10周末PANSS总减分率、阳性症状减分率的差异均有显著性(均P <0 0 5 )。结论 DRD3基因ser9gly功能多态性可能是精神分裂症初发期患者精神症状严重程度和抗精神病药疗效 (尤其对阳性症状疗效 )的遗传影响因子。

Objective To determine whether the dopamine D 3 receptor (DRD3) gene ser9gly polymorphism was associated with the severity of psychotic symptoms and early response to antipsychotics (APS) in schizophrenia Methods A total of 108 first episode Chinese Han schizophrenic patients was recruited Genotyping was performed using the PCR RFLP techniques The Positive and Negative Symptom Scale (PANSS) was used for the evaluation of the severity of psychotic symptoms before and after 10 week treatment with chlorpromazine or risperidone Results There was no significant deviation from Hardy Weinberg equilibrium for DRD3 genotypes in all patients′ group and gender subgroups (all P> 0 05) The distribution of genotypes between the responders and non responders groups was significantly different (χ 2=6 44, ν=2, P< 0 05) There were no significant differences on clinical features between the subgroups of genotypes (all P> 0 05) The DRD3 genotype was significantly associated with the reduction rates in both the PANSS total ( P< 0 05) and positive subscale scores ( P< 0 05) after 10 weeks APS treatment Conclusions DRD3 ser9gly functional polymorphism is possibly associated with the severity of psychotic symptoms in first episode schizophrenic patients as well the short term response to antipsychotics