title: Pharmacogenomics in Pediatric Patients: Towards Personalized Medicine.
abstract: It is well known that drug responses differ among patients with regard to dose requirements, efficacy, and adverse drug reactions (ADRs). The differences in drug responses are partially explained by genetic variation. This paper highlights some examples of areas in which the different responses (dose, efficacy, and ADRs) are studied in children, including cancer (cisplatin), thrombosis (vitamin K antagonists), and asthma (long-acting β2 agonists). For childhood cancer, the replication of data is challenging due to a high heterogeneity in study populations, which is mostly due to all the different treatment protocols. For example, the replication cohorts of the association of variants in TPMT and COMT with cisplatin-induced ototoxicity gave conflicting results, possibly as a result of this heterogeneity. For the vitamin K antagonists, the evidence of the association between variants in VKORC1 and CYP2C9 and the dose is clear. Genetic dosing models have been developed, but the implementation is held back by the impossibility of conducting a randomized controlled trial with such a small and diverse population. For the long-acting β2 agonists, there is enough evidence for the association between variant ADRB2 Arg16 and treatment response to start clinical trials to assess clinical value and cost effectiveness of genotyping. However, further research is still needed to define the different asthma phenotypes to study associations in comparable cohorts. These examples show the challenges which are encountered in pediatric pharmacogenomic studies. They also display the importance of collaborations to obtain good quality evidence for the implementation of genetic testing in clinical practice to optimize and personalize treatment.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Hedy
authors.initials: H
authors.lastname: Maagdenberg
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Susanne J H
authors.initials: SJ
authors.lastname: Vijverberg
authors.affiliation: Department of Pediatric Hematology and Stem Cell Transplantation, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bierings
authors.affiliation: Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC, Canada.|Department of Pediatrics, Faculty of Medicine, University of British Columbia, 4480 Oak Street, Vancouver, BC, Canada.|Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, 4480 Oak Street, Vancouver, BC, Canada.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: Department of Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.
authors.forename: Hubertus G M
authors.initials: HG
authors.lastname: Arets
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. a.h.maitland@uu.nl.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D001249:Asthma / Q000188:drug therapy; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D003362:Cost-Benefit Analysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D057285:Precision Medicine; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D002945:Cisplatin