A Study on the Association between Polymorphism in Dopamine D_4 Receptor Gene and Psychiatric Diseases

多巴胺D_4受体基因多态性与精神疾病相关性研究

• 批准号: 05670797
• 负责人: FUKUDA Masato
• 金额: $ 0.83万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670797/
• 关键词: dopamine receptor,; D_4 receptor gene,; psychiatric disease,; DNA polymorphism,; polymerase chain reaction (PCR); 遺伝子多型; D_4受容体; 多型性

Dopaminergic system are assumed to play an important role in the etiology and the pathophysiology of many psychiatric diseases. Among five types of human dopamine receptors, cDNA polymorphism with repeated sequences has been demonstrated in D_4 receptor gene. The purpose of this syudy is 1) to establish an easy method to determine the polymorphism in D_4 receptor gene using white blood cell DNA,and 2) to investigate the association between the polymorphism and psychiatric diseases.In 1993, amplification of D_4 receptor gene was conducted with polymerase chain reaction (PCR) method using three sets of primers. Specific amplification of D_4 receptor was unsuccessful because many other genes were amplified simultaneously. Survey of the relevant literatures showed that D_4 receptor gene is one of the most difficult one to be amplified by PCR.In 1994, single band in the electrophoresis of PCR products was obtained with many technical improvement and PCR condition adjustment. The band probably represent the intended D_4 receptor gene because the band showed the same electrophoretic Pattern as that of D_4 receptor gene when digested by two different restriction enzymes. Therefore, the D_4 receptor gene is easily amplified with PCR method under the condition determined here. Now, the association between D_4 receptor gene polymorphism and psychiatric diseases is being investigated with the above method.

多巴胺能系统被认为在许多精神疾病的病因学和病理生理学中起重要作用。在人类五种多巴胺受体中，D_4受体基因存在重复序列的cDNA多态性。本研究的目的是：1）建立一种利用白色血细胞DNA检测D_4受体基因多态性的简便方法; 2）探讨该多态性与精神疾病的关系。1993年，采用三组引物，采用聚合酶链反应（PCR）方法对D_4受体基因进行了扩增。D_4受体的特异性扩增不成功，因为许多其他基因同时扩增。综述有关文献表明，D_4受体基因是PCR扩增最困难的基因之一，1994年经过多次技术改进和PCR条件调整，PCR产物电泳出现单一条带。这条酶切带与D_4受体基因的酶切图谱相同，可能代表D_4受体基因。因此，在所确定的条件下，用PCR方法很容易扩增D_4受体基因。目前，D_4受体基因多态性与精神疾病的相关性研究正在进行中。