Theravance Biopharma US, Inc., South San Francisco, CA, USA.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Drug Metab Rev. 2021 May;53(2):253-278. doi: 10.1080/03602532.2021.1909613. Epub 2021 May 17.
Pharmacogenetic research has resulted in the identification of a multitude of genetic variants that impact drug response or toxicity. These polymorphisms are mostly common and have been included as actionable information in the labels of numerous drugs. In addition to common variants, recent advances in Next Generation Sequencing (NGS) technologies have resulted in the identification of a plethora of rare and population-specific pharmacogenetic variations with unclear functional consequences that are not accessible by conventional forward genetics strategies. In this review, we discuss how comprehensive sequencing information can be translated into personalized pharmacogenomic advice in the age of NGS. Specifically, we provide an update of the functional impacts of rare pharmacogenetic variability and how this information can be leveraged to improve pharmacogenetic guidance. Furthermore, we critically discuss the current status of implementation of pharmacogenetic testing across drug development and layers of care. We identify major gaps and provide perspectives on how these can be minimized to optimize the utilization of NGS data for personalized clinical decision-support.
药物遗传学研究已经确定了许多影响药物反应或毒性的遗传变异。这些多态性大多是常见的，并且已经作为可操作的信息包含在许多药物的标签中。除了常见的变异之外，下一代测序（NGS）技术的最新进展已经确定了大量罕见的、具有特定人群的药物遗传学变异，这些变异的功能后果尚不清楚，传统的正向遗传学策略无法检测到。在这篇综述中，我们讨论了如何在 NGS 时代将全面的测序信息转化为个性化的药物基因组学建议。具体来说，我们提供了对罕见药物遗传学变异性的功能影响的最新更新，以及如何利用这些信息来改善药物遗传学指导。此外，我们批判性地讨论了药物遗传学检测在药物开发和护理各个层面的实施现状。我们确定了主要的差距，并就如何最小化这些差距以优化 NGS 数据在个性化临床决策支持中的利用提供了观点。
