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等位基因变异对抗抑郁药和抗精神病药反应表型的贡献。

Contribution of allelic variations to the phenotype of response to antidepressants and antipsychotics.

作者信息

Maier Wolfgang, Zobel Astrid

机构信息

Klinik und Poliklinik für Psychiatrie und Psychotherapie, der Universität Bonn, Sigmund-Freud-Str 25, Bonn, Germany.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2008 Mar;258 Suppl 1:12-20. doi: 10.1007/s00406-007-1004-z.

Abstract

Individualized medicine through molecular pharmacogenetics is one of the major future goals in clinical medicine. In psychopharmacology, pharmacogenetics became an expanding research component. Major research results were already attained: first, it is now feasible to predict a major proportion of the interindividual variation of plasma levels of most antidepressants and antipsychotics by using the DNA-sequence variation in genes for crucial CYP P450-enzymes as CYP2D6. Second, it is now possible to relate serious side effects (tardive dyskinesia, weight gain) of antipsychotics to specific genetic variants of genes for target proteins. Third, a long list of mainly functional variants in target protein genes was explored for their predictive power for the beneficial and adverse treatment outcome. Although specific results transferable into clinical practice were not yet obtained in this respect, the proof of principle could be demonstrated.

摘要

通过分子药物遗传学实现个体化医疗是临床医学未来的主要目标之一。在精神药理学中,药物遗传学已成为一个不断扩展的研究领域。已经取得了一些主要研究成果:首先,利用关键CYP P450酶(如CYP2D6)基因中的DNA序列变异,现在可以预测大多数抗抑郁药和抗精神病药血浆水平个体间变异的很大一部分。其次,现在有可能将抗精神病药的严重副作用(迟发性运动障碍、体重增加)与靶蛋白基因的特定遗传变异联系起来。第三,对靶蛋白基因中一长串主要的功能变异进行了研究,以探讨它们对治疗有益和不良结果的预测能力。尽管在这方面尚未获得可转化为临床实践的具体结果,但已证明了其原理。

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