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

多巴胺能系统在许多精神疾病的病因和病理生理中起着重要的作用。在人类5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)建立一种利用白细胞DNA检测D_4受体基因多态性的简便方法；2)探讨该基因多态性与精神疾病的关系。1993年，用三组引物对D_4受体基因进行了PCR扩增。由于同时扩增了许多其他基因，因此无法对D_4受体进行特异性扩增。查阅相关文献发现，D_4受体基因是PCR扩增难度最大的基因之一。1994年，经过多次技术改进和PCR条件调整，获得了PCR产物的单带电泳。这条条带可能代表了D_4受体基因，因为这条条带在两种不同的限制性内切酶酶切时显示出与D_4受体基因相同的电泳模式。因此，在这里确定的条件下，用PCR方法很容易扩增到D_4受体基因。目前，人们正利用上述方法研究D_4受体基因多态性与精神疾病的关系。

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.