Division of Psychiatry Research, Department of Psychiatry, The Zucker Hillside Hospital, 75-59 263rd St., Glen Oaks, NY 11004, USA.
Am J Psychiatry. 2010 Jul;167(7):763-72. doi: 10.1176/appi.ajp.2009.09040598. Epub 2010 Mar 1.
Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D(2)) receptor blockade. Therefore, it seems plausible that variation in the DRD(2) gene is associated with clinical response to antipsychotic drug treatment. The authors conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response.
A MEDLINE search of articles available up to December 31, 2008, yielded 18 prospective studies examining DRD2 gene variation and antipsychotic response in schizophrenia patients; of which, 10 independent studies met criteria for inclusion. Clinical response to antipsychotic treatment was defined as a 50% reduction of either the Brief Psychiatric Rating Scale total score or Positive and Negative Syndrome Scale total score at approximately 8 weeks of follow-up evaluation. Odds ratio was the primary effect-size measure and computed for each polymorphism in each study. Sufficient data were available for two DRD2 polymorphisms: -141C Ins/Del and Taq1A.
Six studies reported results for the -141C Ins/Del polymorphism (total sample size: N=687). The Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Eight studies assessed the Taq1A polymorphism and antipsychotic response (total sample size: N=748). There was no significant difference in the response rate among A1 allele carriers relative to individuals with the A2/A2 genotype or A2 allele carriers relative to individuals with the A1/A1 genotype.
The DRD2 genetic variation is associated with clinical response to antipsychotic drug treatment. These data may provide proof-of-principle for pharmacogenetic studies in schizophrenia.
有几条证据表明，抗精神病药物的疗效是通过多巴胺 D2（D2）受体阻断来介导的。因此，似乎可以合理地认为，DRD2 基因的变异与抗精神病药物治疗的临床反应有关。作者进行了首次荟萃分析，以检验 DRD2 多态性与抗精神病药物反应之间的关系。
对截至 2008 年 12 月 31 日的文章进行了 MEDLINE 搜索，共获得了 18 项研究，这些研究检查了精神分裂症患者的 DRD2 基因变异与抗精神病药物反应之间的关系；其中，有 10 项独立研究符合纳入标准。抗精神病药物治疗的临床反应定义为在大约 8 周的随访评估时，简明精神病评定量表总分或阳性和阴性综合征量表总分降低 50％。比值比是主要的效应量指标，并且针对每个研究中的每个多态性进行了计算。对于两个 DRD2 多态性，-141CIns/Del 和 Taq1A，有足够的数据。
有 6 项研究报告了 -141CIns/Del 多态性的结果（总样本量：N=687）。与 Ins/Ins 基因型相比，Del 等位基因携带者与抗精神病药物反应较差显著相关。有 8 项研究评估了 Taq1A 多态性与抗精神病药物反应（总样本量：N=748）。A1 等位基因携带者与 A2/A2 基因型个体或 A2 等位基因携带者与 A1/A1 基因型个体的反应率之间没有显着差异。
DRD2 基因变异与抗精神病药物治疗的临床反应有关。这些数据可能为精神分裂症的药物遗传学研究提供了初步证据。
