Drug Metabolism and Toxicity: Influence of Genetic and Epigenetic Factors



July 21, 2011

Pharmacogenomic research has focused on understanding the molecular mechanisms behind Adverse Drug Reactions (ADRs) and finding biomarkers that identify people at risk as well as finding genetic causes to altered efficacy of drugs. Serious ADRs have been shown to cause/contribute to 6‑7% of all hospitalisations, a 2 day increase in average length of hospitalisation, 100,000 deaths annually in the US and, may according to some estimations have a similar cost as the drug treatment itself . During recent years the number of reported ADRs and ADR-related fatalities have actually increased, both by about 2.6-fold. At least 34 drugs were withdrawn from the market during 1995-2006, mainly due to hepatotoxic or cardiotoxic effects.The interindividual differences in drug metabolism are extensive. At present we do understand a major part of the true genetic reasons to such variability as copy number variations, in/dels and SNPs. Such differences can be explained by epigenetic factors such as DNA methylation, post-translational modification of histones and expression of ncRNAs such as microRNAs and RNAs.The lecture will give an update in the field of genetic polymorphism and epigenetics of genes of important for prediction of drug metabolism and ADRs focusing on clinically relevant examples.

Drug Discovery

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