D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.
D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.
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DOI：
10.1176/appi.ajp.2009.09040598
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Malhotra AK
中科院分区：
文献类型：
--
作者：
Zhang JP;Lencz T;Malhotra AK
一些证据表明，抗精神病药物的疗效是通过阻断多巴胺D2受体介导的。因此，DRD2基因的变异似乎与抗精神病药物治疗的临床反应有关。我们进行了第一次荟萃分析，以检验DRD2基因多态与抗精神病药物反应的关系。Medline搜索(2008年12月31日)共产生18项前瞻性研究，研究精神分裂症患者的DRD2变异和抗精神病药物反应，其中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被定义为在大约8周的随访中BPRS或PANSS总分减少50%。优势比(OR)是主要的效应大小测量，并在每项研究中计算每个基因的多态。有足够的数据支持DRD2的两个多态，-141C Ins/Del和Taq1A。有6项研究报道了-141C Ins/Del多态的结果(n=698)。与INS/INS基因相比，Del等位基因携带者与较差的抗精神病药物反应显著相关，OR=.65，p=.03。有8项研究评估了Taq1A基因多态和抗精神病药物反应(n=748)。A1携带者与A2/A2或A2携带者与A1/A1携带者的应答率无显著差异。DRD2基因变异与抗精神病药物治疗的临床反应有关。这一数据可能为精神分裂症的药物遗传学研究提供原则证据。
Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine D2 receptor blockade. Therefore, it seems plausible that variation in the DRD2 gene is associated with clinical response to antipsychotic drug treatment. We conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response. Medline search (12/31/2008) yielded 18 prospective studies examining DRD2 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 BPRS or PANSS total score at approximately 8 weeks follow-up. Odds ratio (OR) was the primary effect size measure and was computed for each polymorphism in each study. Sufficient data were available for two DRD2 polymorphisms, -141C Ins/Del and Taq1A. Six studies reported results on the -141C Ins/Del polymorphism (n=698). The Del allele carrier was significantly associated with poorer antipsychotic drug response, compared to the Ins/Ins genotype, OR=.65, p=.03. Eight studies assessed the Taq1A polymorphism and antipsychotic response (n=748). There was no significant difference in response rate in A1 carrier vs. A2/A2 genotype or A2 carrier vs. A1/A1 genotype. DRD2 genetic variation is associated with clinical response to antipsychotic drug treatment. This data may provide proof-of-principle for pharmacogenetic studies in schizophrenia.
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影响因子：
17.7
作者：
Lencz, T;Robinson, DG;Malhotra, AK
通讯作者：
Malhotra, AK
DOI：
10.1176/appi.ajp.2009.08091445
发表时间：
2009-07
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Ghose S;Gleason KA;Potts BW;Lewis-Amezcua K;Tamminga CA
通讯作者：
Tamminga CA
影响因子：
11
作者：
Jönsson, EG;Nöthen, MM;Sedvall, GC
通讯作者：
Sedvall, GC
影响因子：
168.9
作者：
Kahn, Rene S.;Fleischhacker, W. Wolfgang;Grobbee, Diederick E.
通讯作者：
Grobbee, Diederick E.
影响因子：
3.7
作者：
Duval, S;Tweedie, R
通讯作者：
Tweedie, R