Vanakker O M, De Paepe A
Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Int J Pediatr. 2013;2013:136524. doi: 10.1155/2013/136524. Epub 2013 Jan 17.
Pharmacogenetics is considered as a prime example of how personalized medicine nowadays can be put into practice. However, genotyping to guide pharmacological treatment is relatively uncommon in the routine clinical practice. Several reasons can be found why the application of pharmacogenetics is less than initially anticipated, which include the contradictory results obtained for certain variants and the lack of guidelines for clinical implementation. However, more reproducible results are being generated, and efforts have been made to establish working groups focussing on evidence-based clinical guidelines. For another pharmacogenetic hurdle, the speed by which a pharmacogenetic profile for a certain drug can be obtained in an individual patient, there has been a revolution in molecular genetics through the introduction of next generation sequencing (NGS), making it possible to sequence a large number of genes up to the complete genome in a single reaction. Besides the enthusiasm due to the tremendous increase of our sequencing capacities, several considerations need to be made regarding quality and interpretation of the sequence data as well as ethical aspects of this technology. This paper will focus on the different NGS applications that may be useful for pharmacogenomics in children and the challenges that they bring on.
药物遗传学被视为当今个性化医疗如何付诸实践的一个典型例子。然而,在常规临床实践中,用于指导药物治疗的基因分型相对并不常见。对于药物遗传学应用未达最初预期的情况,可以找到几个原因,其中包括某些变异体得出的相互矛盾的结果以及临床实施缺乏指导原则。然而,正在产生更多可重复的结果,并且已努力建立专注于循证临床指南的工作组。对于另一个药物遗传学障碍,即在个体患者中获得某种药物的药物遗传学概况的速度,通过引入下一代测序(NGS),分子遗传学领域发生了一场革命,使得在单个反应中对大量基因甚至整个基因组进行测序成为可能。除了因测序能力大幅提高而带来的热情之外,还需要在序列数据的质量和解读以及该技术的伦理方面进行若干考量。本文将重点关注可能对儿童药物基因组学有用的不同NGS应用及其带来的挑战。