精神分裂症儿茶酚氧位甲基转移酶功能基因多态性研究

Association of negative symptoms with catechol-O-methyl transferase functional polymorphism in untreated schizophrenic patients

目的 :分析儿茶酚氧位甲基转移酶 (COMT)功能基因多态性与精神分裂症患者精神症状严重程度和抗精神病药急性期治疗疗效的相关性。 方法 :采用多聚酶链反应 限制性内切酶片断长度多态性技术 (PCR RFLP)方法分析 138例首次治疗的精神分裂症患者COMT基因缬氨酸 (Val) 15 8蛋氨酸(Met)功能多态性 ;采用阳性症状和阴性症状量表 (PANSS)评定患者治疗前后精神症状 ,并分析等位基因和基因型与临床指标、治疗前PANSS分值及治疗 10周后PANSS减分率的相关性。 结果 :COMTVal15 8Met基因型在患者组和男女亚组的分布频率均符合Hardy Weinberg定律 ;等位基因和基因型在治疗显效组和未显著进步组分布频率差异均无显著性 ;各基因型亚组及是否携带Met等位基因亚组的临床指标差异均无显著性 ;基因型与治疗前PANSS总分和阴性症状分显著相关 ,而与PANSS总减分率和各分值减分率无显著相关。 结论 :COMTVal/Val基因型主要与首次治疗精神分裂症患者阴性症状相关 ,支持COMTVal等位基因是精神分裂症脑前额皮质多巴胺功能低下的遗传影响因子的研究发现。

Objective:To investigate whether COMT gene Val 158 Met functional polymorphism associating with the symptomatic severity and acute therapeutic response to antipsychotics (APS) in schizophrenia. Method:Genotyping was performed using the PCR-RFLP techniques in a total of 138 untreated schizophrenic patients.The positive and negative symptom scale (PANSS) was used for the evaluation of the severity and the improvement of psychotic symptoms. Results:There is no significant deviation from Hardy Weinberg equilibrium for COMT genotypes in all groups.There are no significant differences in distribution of either alleles or genotypes between the responders and non-responders groups. There is no significant difference in clinical features between genotype groups. The COMT genotype is significantly associated with the severity of psychotic symptoms either in baseline total PANSS or in negative symptom but not with the percentage improvement of PANSS scores after 10 weeks treatment. Conclusion:COMT Val/Val genotype is associated with the severity of psychotic symptoms in untreated schizophrenic patients,particularly with negative symptoms,further suggesting that the COMT functional polymorphism affect dopamine neurotransmission of prefrontal cortex of schizophrenia.