Pharmacogenomics and its implications for autoimmune disease

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 ten leading causes of death and illness in the developed world with direct medical costs of US$137–177 billion annually in the USA. Although many factors influence the effect of medications (i.e. age, organ function, drug interactions), genetic factors account for 20–95% 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 adverse drug reactions. Pharmacogenomics has led to several genetic tests that provide clinical dosing recommendations. For autoimmune disease, pharmacogenomics has led to several DNA-based tests to improve drug selection, optimize dosing, and minimize the risk of toxicity. The ‘GATC’ project is a nation-wide project established in Canada to identify novel predictive genomic markers of severe ADRs in children. An ADR surveillance network has been established in all 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, collect DNA samples, and apply genomics-based technologies to identify ADR-associated genetic markers.