Genotypic Approaches to Therapy in Children

Abstract

A striking failure of modern medicine is the debilitating and lethal consequences of adverse drug reactions (ADRs), which rank as one of the top 10 leading causes of death and illness in the developed world with direct medical costs of 137-177 billion annually US dollars in the USA. Although many factors influence the effect of medications (e.g., age, organ function, drug interactions), genetic factors account for 20% to 95% of drug response variability and play a significant role in the incidence and severity of ADRs. The field of pharmacogenomics seeks to identify genetic factors responsible for individual differences in drug efficacy and ADRs. Pharmacogenomics has led to several genetic tests that provide clinical dosing recommendations. The Genetic Approaches to Therapy in Children (GATC) project is a national project established in Canada to identify novel predictive genomic markers for severe ADRs in children. An ADR surveillance network has been established in eight of Canada's major children's hospitals, serving up to 75% of all Canadian children. The goal of the project is to identify patients experiencing specific ADRs and matched controls, collect DNA samples, and apply genomics-based technologies to identify ADR-associated genetic markers with the goal of preventing serious ADRs in susceptible children.

Application of principal component analysis to pharmacogenomic studies in Canada

“…A total of 524 patient DNA samples were then analyzed as part of the GATC project, a national project established in Canada to identify novel predictive genomic markers of severe ADRs in children 14 . Patients who suffered any serious ADR were enrolled as well as drug-matched controls.…”

Researchers’ Perceptions of the Ethical Implications of Pharmacogenomics Research with Children

“…This research has the potential to optimize drug development and drug therapy and to reduce the risks of adverse drug reactions [1,2,3]. In addition, the application of pharmacogenomics promises to reduce the costs associated with health care services [4,5,6].…”

Pharmakogenomik

“…Alarmierende Daten weisen darauf hin, dass unerwünschte Arzneimittelwirkungen (UAW) zu den Top 10 der füh-renden Todesursachen in der industrialisierten Welt gehören [21] [21]. Ein UAW-Überwa-chungsnetzwerk versucht, alle UAW bei Kindern in 8 kanadischen Kinderkrankenhäusern, in denen insgesamt etwa 75% aller hospitalisierten Kinder in Kanada betreut werden, zu erfassen.…”

“…Ein UAW-Überwa-chungsnetzwerk versucht, alle UAW bei Kindern in 8 kanadischen Kinderkrankenhäusern, in denen insgesamt etwa 75% aller hospitalisierten Kinder in Kanada betreut werden, zu erfassen. Im Sinne einer Fall-Kontroll-Studie wird dann versucht, mit Hilfe eines SNP-GenotypingAssays (dieser enthält 1536 HapMap-Marker-SNP und 1536 funktionelle SNP) genomische Determinanten für wichtige schwere UAW zu identifizieren [21]. Damit wird es in absehbarer Zeit hoffentlich möglich sein, zumindest die sehr schweren UAW basierend auf einem genetischen Test a priori zu verhindern.…”