Pharmacogenomics in Practice.
Pharmacogenomics in Practice.
复制标题
药物基因组学实践。
DOI：
10.1002/cpt.1600
复制
发表时间：
2019
影响因子：
6.7
通讯作者：
Weinshilboum,Richard
中科院分区：
文献类型：
--
作者：
Wang,Liewei;Weinshilboum,Richard
药物基因组学是临床基因组学的一个重要方面，涉及越来越多的患者。这是因为药物基因组学检测正以越来越快的速度应用于临床护理最初主要是在学术医疗中心，但也遍及医疗保健系统。本评论描述了药物基因组学在一个大型的综合学术医疗系统中的广泛应用，重点是已经和正在解决的挑战和已经吸取的教训。药物基因组学是临床基因组学的一个方面，最终将有最广泛的应用，最终触及每一个病人。药物基因组学已经从早期的候选基因（通常是编码药物代谢酶的基因）的药物遗传学研究发展成为应用全基因组技术的药物基因组学，该技术使得可以以无偏的方式扫描整个基因组以识别单核苷酸多态性和基因（通常是非预期的基因），这些基因有助于药物反应的变化。对药物基因组学某些方面的临床应用，如TPMT和DPYD多态性，美国的临床药物遗传学实施联盟（CPIC）和欧洲的荷兰药物遗传学工作组等团体为药物遗传学的临床实施建立了客观的指导方针，这有助于建立必要的同行，回顾了为临床基因组学这一重要方面带来严谨性所需的知识基础设施。因此，在药物基因组学的科学基础不断发展的同时，将临床基因组学的这一重要方面带到床边的挑战也在同时增长。前美国众议院议长奥尼尔（Tip O'Neil）喜欢说：“所有的政治都是地方性的。药物基因组学的临床实施也是如此。每一个学术医疗中心，最终，每一家医院和诊所都需要解决与药物基因组学实施相关的挑战，但始终在其独特的当地环境所建立的边界内。我们一直致力于将药物基因组学应用于我们大型、高度集成的多站点学术医疗中心的每一位患者。在随后的段落中反映的观点是基于这一经验，但它们涉及每个试图将临床基因组学的这一重要方面带到床边的机构所面临的问题。
Pharmacogenomics is an important aspect of clinical genomics that is touching an increasingly large number of patients. That is because pharmacogenomic testing is being implemented into clinical care at an increasing pace—initially primarily within academic medical centers, but also across healthcare systems. This Commentary describes the broad implementation of pharmacogenomics within one large, integrated academic medical system, with a focus on challenges that were and are being addressed and lessons that have been learned.Pharmacogenomics is the aspect of clinical genomics that will eventually have the broadest application—ultimately touching every patient. Pharmacogenomics has evolved from early pharmacogenetic studies of candidate genes, often genes that encoded drug metabolizing enzymes, to become pharmacogenomics with the application of genome-wide techniques that make it possible to scan across the genome in an unbiased fashion to identify single nucleotide polymorphisms and genes, often unanticipated genes, that contribute to variation in drug response. There can no longer be any doubt of the clinical utility of certain aspects of pharmacogenomics, eg, TPMT and DPYD polymorphisms, and the establishment of objective guidelines for the clinical implementation of pharmacogenomics by groups such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) in the United States and the Dutch Working Group on Pharmacogenetics in Europe—among others—has helped to create the necessary peer-reviewed knowledge infrastructure required to help bring rigor to this important aspect of clinical genomics. As a result, in parallel with the growth of the scientific foundation for pharmacogenomics, a discipline that continues to evolve rapidly, challenges associated with bringing this important aspect of clinical genomics to the bedside have grown in parallel. Former Speaker of the United States House of Representatives “Tip” O’Neil was fond of saying that “all politics are local.” The same is true of pharmacogenomic clinical implementation. Every academic medical center and, eventually, every hospital and clinic will need to address challenges associated with pharmacogenomic implementation, but always within boundaries established by their unique local environments. We have been deeply involved in attempts to bring pharmacogenomics into the practice for every patient seen in our large, highly integrated multiple-site academic medical center. The perspectives reflected in subsequent paragraphs are based on that experience, but they involve issues faced by every institution attempting to bring this important aspect of clinical genomics to the bedside.