한국인 정신분열병 환자에서 항정신병 약물의 치료 반응과 도파민 D2, D3 및 D4 수용체 유전자 다형성
The relationship between the therapeutic response to antipsychotic drugs and the dopamine D2, D3, and D4 receptor gene polymorphisms in Korean schizophrenic patients
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초록
항정신병 약물의 치료 반응을 예측해 줄 수 있는 유전자 지표를 찾기 위한 최근의 많은 약물유전학 연구들은 일관된 결과를 보고하지 못하고 있다. 본 연구는 항정신병 약물의 치료 반응과 도파민 D2, D3 및 D4 수용체 유전자 다형성과 관련성을 조사하였다.연구 대상은 18～60세에 해당되면서 정신분열병의 DSM-IV 진단기준을 만족하고 본 연구에 대해 서면 동의한 국립부곡병원의 입원 환자 200명이었다. 연구는 대상자들의 입원 당시 병록지를 검토하여 후향적으로 이루어졌다. 대상자들은 퇴원할 당시를 기준으로 약물치료 반응 정도에 따라 ‘반응군’과 ‘비반응군’으로 구분되었으며 양군사이의 도파민 수용체 유전자 다형성 차이를 비교하였다.대상자 200명 중에서 188명(94%)이 비전형 항정신병 약물을 사용하였고 반응군은 141명(70.5%)이었다. 도파민 D2 수용체 유전자 Ser311Cys 다형성, 도파민 D3 수용체 유전자 Ser9Gly 다형성, 도파민 D4 수용체 유전자 exon Ⅲ의 48개 염기반복 다형성에서 반응군과 비반응군 사이의 대립유전자 및 유전자형 빈도의 차이를 보이지 않았다.
Abstract
Objectives : A considerable number of pharmacogenetic studies have been performed in recent years to define the association of antipsychotic drug response with dopamine receptor polymorphisms. The purpose of this study was to investigate the relationship between the therapeutic response to antipsychotic drugs and the polymorphisms of the dopamine D2, D3, and D4 receptor genes (DRD2, DRD3 and DRD4, respectively). Methods : We conducted retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia (DSM-IV) treated with various antipsychotics (94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, responders and non-responders, by responsiveness to antipsychotic drugs according to a four-point scale used in previous studies; responders included moderate to marked responded patients and non-responders included none to minimal responded patients. We analyzed the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4.Results : Among the total patients of 200, 141 (70.5%) were categorized as responders. There were no significant differences in the frequencies of the DRD2, DRD3, and DRD4 alleles and genotypes between responders and non-responders.Conclusion : These results suggest that the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4 are not associated with the therapeutic response to antipsychotic drugs in Korean schizophrenic patients. A larger prospective study is needed to elucidate the association between antipsychotic response and dopamine receptor gene polymorphism.
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