%0 Journal Article
%T Pharmacogenomics in Children: Advantages and Challenges of Next Generation Sequencing Applications
%A O. M. Vanakker
%A A. De Paepe
%J International Journal of Pediatrics
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/136524
%X 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. 1. Introduction Pharmacogenetics refers to the influence of DNA variants on drug response, the knowledge of which can facilitate selection of the optimal drug, dose, and treatment duration and avert adverse drug reactions [1]. Several demonstrations have been given on the differences in response to drugs between children and adults [2]. These include differences in drug metabolism and gene expression, the latter being a highly dynamic process functioning from the neonatal period over childhood into adult life. Though the number of studies specifically devoted to the pediatric population is still limited compared to adults, an increasing number of genes are being identified in which variants have an influence on pharmacological treatment of childhood diseases [3]. The identification of variants in novel genes as well as the validation of their functional effects will further increase our ability to predict drug treatment response in children; at the same time, the clinical implementation of this knowledge will demand an efficient diagnostic approach to first identify a pharmacogenomic profile in an individual patient in a short period of time, next to evidence-based clinical guidelines to facilitate decision making based on the
%U http://www.hindawi.com/journals/ijpedi/2013/136524/