Adverse Drug Reactions
Severe adverse drug reactions (ADRs) are the fourth leading cause of death and illness in the developed world, claiming tens of thousands of lives and costing billions of dollars in direct medical costs each year. In Canada alone, there are an estimated 200,000 severe ADRs, claiming 10,000 to 22,000 lives, and costing $13.7 to $17.7 billion each year.
Although many factors influence the effects of medication, such as age, body mass, organ function, and drug interactions, genetic factors can account for up to 95% of drug-response variability and susceptibility to a significant number of severe ADRs.
By scanning and analyzing the genomes of ADR sufferers and comparing them to the genomes of those who exhibit no adverse reaction to a specific drug, we aim to find the genetic mutations that can cause these severe ADRs. In 2006, we became a leading member of the Canadian Pharmacogenomics Network for Drug Safety project, a nation-wide sustainable research program that aims to identify genetic markers that are predictive of severe ADRs and implement these in cost-effective diagnostic screening programs to reduce the occurrence of permanent disability and deaths from severe ADRs.
This year, we are significantly expanding its Pharmacogenomics research efforts by building a brand new, dedicated facility capable of high-throughput genome sequencing. To complement this resource, our bioinformatics teams are developing the laboratory data management and analysis tools that we will need to study genetic variation associated with differential responses to medication. With these resources, research aim to uncover the genetic cause of cisplatin-induced deafness in children, anthracycline-induced cardiotoxicity in oncology, and codeine-induced infant mortality.
Madadi P, Ross CJ, Hayden MR, Carleton BC, Gaedigk A, Leeder JS, Koren G. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin. Pharmacol. Ther. 85(1):31-5. (2009) PMID 18719619
Ross CJ, Carleton B, Warn DG, Stenton SB, Rassekh SR, Hayden MR. Genotypic approaches to therapy in children: a national active surveillance network (GATC) to study the pharmacogenomics of severe adverse drug reactions in children. Ann. N. Y. Acad. Sci. (2007) PMID 17911433