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.