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突破成瘾的基因组学和药物遗传学障碍。

Breaking barriers in the genomics and pharmacogenetics of drug addiction.

机构信息

Centre for Addiction & Mental Health, Department of Psychiatry, Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.

出版信息

Clin Pharmacol Ther. 2010 Dec;88(6):779-91. doi: 10.1038/clpt.2010.175. Epub 2010 Oct 27.

Abstract

Drug addiction remains a substantial health issue with limited treatment options currently available. Despite considerable advances in the understanding of human genetic architecture, the genetic underpinning of complex disorders remains elusive. On the basis of our current understanding of neurobiology, numerous candidate genes have been implicated in the etiology and response to treatment for different addictions. Genome-wide association (GWA) studies have also identified novel targets. However, replication of these studies is often lacking, and this complicates interpretation. The situation is expected to improve as issues such as phenotypic characterization, the apparent "missing heritability," the identification of functional variants, and possible gene-environment (G × E) interactions are addressed. In addition, there is growing evidence that genetic information can be useful in refining the choice of addiction treatment. As genetic testing becomes more common in the practice of medicine, a variety of ethical and practical challenges, some of which are unique to drug addiction, will also need to be considered.

摘要

药物成瘾仍然是一个严重的健康问题,目前可用的治疗选择有限。尽管人类遗传结构的理解取得了相当大的进展,但复杂疾病的遗传基础仍然难以捉摸。基于我们目前对神经生物学的理解,许多候选基因已被牵连到不同成瘾的病因和对治疗的反应中。全基因组关联 (GWA) 研究也确定了新的靶点。然而,这些研究的复制往往缺乏,这使得解释变得复杂。随着解决表型特征、明显的“遗传缺失”、功能性变异的识别以及可能的基因-环境 (G × E) 相互作用等问题,情况预计会有所改善。此外,越来越多的证据表明,遗传信息可以有助于精确定制成瘾治疗的选择。随着基因检测在医学实践中变得越来越普遍,各种伦理和实际挑战也需要考虑,其中一些是成瘾特有的。

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