多巴胺受体与5-羟色胺2A受体基因多态性与迟发性运动障碍的关联分析

Association between the dopamine D_2 、dopamine D_3 、serotonin 2A receptor gene and tardive dyskinesia in chronic schizopnrenia

目的:研究多巴胺D2受体(DRD2)基因TaqI A多态性、多巴胺D3受体(DRD3)基因Ser9G ly功能多态性、5-羟色胺2A(5-HT2A)受体基因A-1438G、T102C多态性与精神分裂症伴发迟发性运动障碍(TD)的相关性。方法:使用异常不自主运动量表(AIMS)评定精神分裂症患者有无TD及TD严重程度。应用聚合酶链反应(PCR)-限制性片段长度多态性(RELP)法分析TD组和非TD组的各受体基因位点的等位基因频率和基因型分布。结果:DRD2基因TaqI A的等位基因频率(P>0.05)和基因型(P>0.05)分布在TD组(n=42)与非TD组(n=52)之间均无显著性差异,且不同基因型间的AIMS总分值差异也无显著性(P>0.05)。DRD3基因Ser9G ly的等位基因频率(P>0.05)和基因型(P=0.08)分布在TD组(n=42)与非TD组(n=52)之间均无显著性差异,且不同基因型间的AIMS总分值差异也无显著性(P>0.05)。5-HT2A受体基因T102C多态性位点与A-1438G为完全连锁不平衡,TD组(n=42)与非TD组(n=51)的基因型总体分布的差异无显著性(P>0.05),等位基因频率分布的差异有显著性(x2=4.36,υ=1,P<0.05)。结论:在中国汉族男性精神分裂症患者中DRD2基因的TaqI A多态性、DRD3功能基因的Ser9G ly多态性可能不是影响TD发生的主要危险因素。5-HT2A受体基因的T102C、A-1438G多态性可能与男性精神分裂症患者的TD相关联。

Objective：The present study was to investigate whether the genetics variation of the dopamine D2 receptor （DRD2） ,dopamine D3 receptor （DRD3） and serotonin 2A receptor（5 -HT2A ）gene was associated with tardive dyskinesia （TD）in chronic schizophrenic patients receiving long- time typical antipsychotics. Methods：42 male schizophrenic Patients with TD, 52 without TD were entered the study. The diagnosis of TD was made according to the Abnormal Involuntary Movement Scale（AIMS） score, with the AIMS score≥3 as having TD. Psychiatric symptoms were rated using the Brief Psychiatric Rating Scale（BPRS）. The receptor gene pol- ymorphism was analyzed with the polymerase chain reaction -restriction fragment length polymorphism. Results： （ 1 ） There were no significant differences in the distributions of the allelic frequencies and genotypes of TaqI A polymorphism of DRD2 gene between the groups （P 〉 0.05 ）. Genotypes of DRD3 gene were not correlated with total AIMS scores in TD patients. （2） There were no significant differences in the distributions of the allelic frequencies and genotypes of Se：gGly polymorphism of DRD3 gene between the groups （ P 〉 0.05）. Genotypes of DRD3 gene were not correlated with total AIMS scores in TD patients. （3） The T102C polymorphism was in complete linkage disequilibrium with the A - 1438G polymorphism. There were no significant differences in the distribution of genotypic of the 5 - HT2A gene between the groups（ P 〉 0.05 ）. A significant excess of C/A allele was in patients with TD compared to those without TD （ c2 = 4.36,v = 1 ,P 〈 0.05 ）. （3）There were no significant differences in clinical demographic characteristics and scores of clinical assessment between the patients with TD and those without TD （ P 〉 0.05 ）. Conclusions ： Our result suggest that the TaqI A polymorphism of DRD2 gene and Se：gGly polymorphism of DRD3 gene may be not a mainly risk factor for the development of TD in Chinese Han male schizophrenia, but the T102C and A - 1438G polymorphism of 5 - HT2A receptor gene may be association with TD in chronic male schizophrenic patients.