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Studies on the brain neurotransmitter-related gene polymorphisms involved in the onset and course of schizophrenia and affective disorders.

脑神经递质相关基因多态性与精神分裂症和情感障碍发病和病程的研究。

基本信息

批准号：
07457207
负责人：
TORU Michio
金额：
$ 4.74万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

Since the potency of antipsychotic drugs correlates with their affinity for the dopamine D2 receptor, this receptor gene might be a most possible caudidate gene for the pathoetiology of schizophrenics. Case-control studies in 419 schizophrenics, 78 patients with affective disorders, 393 patients with alcohol dependence and 579 control subjects on an association of several molecular variants mainly found in the dopamine D2 receptor. The frequency of schizophrenic patients with Cys311 variant was significantly higher particularly in whom without negatic symptoms (17%) when compared with the control (4%) (p<0.00001). This variant was found more frequently in patients with affective disorders with mood-incongruent psychotic features. (33%) (p<0.00001). We found Ins/Del polymorphism at -141C in the 5'region of DRD2 gene. The Del allele frequency was significantly lower in patients with schizophrenia than control subjects (OR : 0.6, p<0.001). Ala677Val polymorphism, which is responsible for the thermolabile methylenetetrahydrofolate reductase deficiency, was significantly more frequently observed in schizophrenic patients (OR : 1.9, p<0.0006).We examined DRD2 gene polymorphism in patients with alcohol dependence. The patients carried Cys311 variant siguificantly more frequently than control (p<0.04). Alcoholic patients had -141 Ins Alle more frequently than controls (p<0.0005). We found that there were more frequent presence of Taq Ia1 allele in DRD2 gene in patients with alcohol dependence (p<0.006).

由于抗精神病药物的效力与其对多巴胺D2受体的亲和力相关，因此该受体基因可能是精神分裂症病因的最可能的尾状核基因。在419名精神分裂症患者，78名情感障碍患者，393名酒精依赖患者和579名对照受试者中进行的病例对照研究，主要是在多巴胺D2受体中发现的几种分子变体的关联。Cys 311变异的频率显著高于对照组（P<0.00001），尤其是在无阴性症状的精神分裂症患者中（17%）。这种变异在具有情绪不一致精神病特征的情感性精神障碍患者中更常见。(33%）（p<0.00001）。在DRD 2基因5 ′端-141 C位点发现了Ins/Del多态性。精神分裂症组Del等位基因频率显著低于对照组（OR：0.6，p<0.001）。Ala 677 Val多态性是导致不耐热的亚甲基四氢叶酸还原酶缺乏的原因，在精神分裂症患者中更常见（OR：1.9，p<0.0006）。Cys 311基因变异的检出率显著高于对照组（P<0.04）。酒精中毒患者比对照组更频繁地具有-141Ins Alle（p<0.0005）。发现DRD 2基因TaqIa 1等位基因在酒依赖组中的频率明显高于对照组（p<0.006）。