DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients
DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients
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DOI：
10.1176/appi.ajp.163.3.529
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发表时间：
2006-03-01
影响因子：
17.7
通讯作者：
Malhotra, AK
中科院分区：
文献类型：
--
作者：
Lencz, T;Robinson, DG;Malhotra, AK
目的：所有抗精神病药物都作用于多巴胺D-2受体。本研究通过检测首发精神分裂症患者的启动子区域变异作为两种一线非典型抗精神病药物反应时间的预测指标，扩展了先前对D-2受体基因(DRD2)的药物遗传学研究。方法：对61例首发精神分裂症患者进行了DRD2基因启动子区A-241G和-141C INS/Del的基因分型，并随机分配接受利培酮或奥氮平治疗16周。用Kaplan-Meier曲线检验稀有等位基因携带者与野生型携带者的持续反应时间。结果：与野生型纯合子相比，G携带者(A-241G)的持续反应时间明显快于野生型纯合子，而-141C Del携带者的反应时间显著延长。结论：D2受体基因的变异可以部分解释首发精神分裂症患者对抗精神病药物临床反应时间的差异。
Objective: All antipsychotics act on the dopamine D-2 receptor. The present study extends prior pharmacogenetic investigations of the D-2 receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics.Method: Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves.Results: Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results.Conclusions: These findings suggest that variation in the D2 receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia.