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首页> 外文期刊>Pharmacogenetics and genomics >Taq1A polymorphism in the dopamine D2 receptor gene predicts brain metabolic response to aripiprazole in healthy male volunteers.
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Taq1A polymorphism in the dopamine D2 receptor gene predicts brain metabolic response to aripiprazole in healthy male volunteers.

机译：多巴胺D2受体基因中的Taq1A多态性预测健康男性志愿者对阿立哌唑的脑代谢反应。

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OBJECTIVE: The Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene has been reported to be associated with the pharmacodynamics of antipsychotic drugs. We investigated the metabolic response of glucose in the brain to aripiprazole in relation to the DRD2 Taq1A polymorphism. METHODS: Twenty healthy male volunteers were recruited and were divided into two groups of 10 participants, according to their DRD2 genotypes (A1A1, n=10; A2A2, n=10). The volunteers received single oral doses of aripiprazole (10 mg) and a placebo, following a single-blind, placebo-controlled, randomized, two-way crossover study design. Brain glucose metabolism was assessed using positron emission tomography, scanned with 18F-fluorodeoxyglucose 12 h after the administration of the drug or placebo. RESULTS: In voxel-based analysis using SPM2, volunteers with the A2A2 genotype showed decreased metabolism in the right middle frontal gyrus, the left middle and inferior frontal gyrus, the right and left inferior temporal gyrus, and the right cingulate gyrus, and increased metabolism in the pons. In contrast, volunteers with the A1A1 genotype exhibited increased metabolism in the right caudate head, and no brain region showed decreased metabolism. In a region-of-interest analysis, significant interactions between drug and genotype were observed in the right medial orbitofrontal gyrus and the left caudate nucleus. CONCLUSIONS: This suggests that DRD2 Taq1A polymorphism status may be associated with the clinical response to aripiprazole.
机译：目的：据报道，多巴胺D2受体（DRD2）基因中的Taq1A多态性与抗精神病药的药效学有关。我们调查了与DRD2 Taq1A多态性相关的阿立哌唑对大脑中葡萄糖的代谢反应。方法：招募了20名健康男性志愿者，根据其DRD2基因型（A1A1，n = 10; A2A2，n = 10）分为两组，每组10名参与者。在单盲，安慰剂对照，随机，双向交叉研究设计之后，志愿者接受了口服阿立哌唑（10 mg）和安慰剂的单次口服剂量。药物或安慰剂给药12小时后，使用正电子发射断层扫描评估脑葡萄糖代谢，用18F-氟脱氧葡萄糖扫描。结果：在使用SPM2的基于体素的分析中，具有A2A2基因型的志愿者显示右中额回，左中和额下回，右和左颞下回，右扣带状回的新陈代谢减少，并且新陈代谢增加在桥上。相反，具有A1A1基因型的志愿者的右尾状头显示出新陈代谢增加，而没有大脑区域显示出新陈代谢下降。在感兴趣区域分析中，在右内侧眶额回和左尾状核中观察到药物和基因型之间的显着相互作用。结论：这表明DRD2 Taq1A多态性状态可能与对阿立哌唑的临床反应有关。

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