Abstract
Objects : Clozapine, prototype of the atypical neuroleptics, was known to have unique antipsychotic effect with a few extrapyramidal effects. While most typical antipsychotic agents mainly block $D_2$ receptors, clozapine has higher affinity for dopamine $D_4$ receptor than for $D_2$ receptor. Many researchers have tried to find out the relationship between schizophrenia and the abnormality of the genes coding dopamine receptors. But no consistent findings were reported. Recently, dopamine $D_4$ receptor was fully sequenced, and the alleles of dopamine $D_4$ receptor gene was found in unusual form on the 48th base pair. Our study was performed to identify the distribution of the dopamine $D_4$ receptor alleles of schizophrenics and normal controls, and whether any difference between the dopamine $D_4$ receptor alleles of schizophrenics and that of normal controls exists. Methods : DNA was extracted from the blood of schizophrenic patients(N=60) and normal controls(N=60). Part of the dopamine $D_4$ receptor gene was amplified by PCR, and amplified DNA was electrophoresed. Authors compared the distribution of the alleles of dopamine $D_4$ receptor gene of normal controls and that of schizophrenic patients. Results : Six kinds of alleles of $D_4$ receptor were observed both groups. The fourth repeat form of alleles was the most common in both schizophrenic patients(75.8%) and normal controls(70.3%), so there was not significant difference between two groups. Conclusion : The Difference in the distribution of the dopamine $D_4$ receptor gene alleles is not thought to be responsible for the pathophysiology of the schizophrenia. However, the difference in the expression of the dopamine $D_4$ receptor gene between normal and schizophrenia is left to be scrutinized.
항정신병 약물인 clozapine이 주로 작용하는 도파민 수용체로 알려진 도파민 $D_4$ 수용체는 각각 50 염기쌍에 해당하는 크기의 차이가 있음이 알려져 PCR을 이용해 정신분열증 환자와 정상대조군을 대상으로 도파민 $D_4$ 수용체 유전자의 대립형질 분포를 알아보았다. 정신분열증 환자군과 대조군 모두에 있어 여섯종류의 대립형질의 관찰되었으며 정신분열증 환자에서 네번 반복형태의 대립형질이 수적으로 더 많이 관찰되었지만 통계적으로 유의한 차이는 없었으며 정신분열증과 관련된 도파민 $D_4$ 수용체 유전자의 대립형질은 확인되지 않았다. 그러나 보다 객관적인 정보를 얻기 위해서 clozapine에 대한 반응에 따라 정신분열증 환자의 아형을 분류하고 그 아형에 따른 도파민 $D_4$ 수용체 유전자 대립형질분포의 차이에 관한검증이 필요하며, 나아가 도파민 $D_4$ 수용체 유전자의 발현에 있어 정신분열증 환자와 정상인에 차이가 있는지 여부를 밝히는 추적연구가 필요할 것으로 사료된다.