Genetic and Epigenetic Factors Affecting Cytochrome P450 Phenotype and Their Clinical Relevance

Pharmacogenetics (or pharmacogenomics) studies the role of inherited and acquired genetic variation in drug response. Clinically relevant pharmacogenetic examples, mainly involving drug metabolism are known for decades, but the field was not evolved until the 1970s, when the discovery of the CYP2D6 polymorphism and its resultant effect on drug toxicity and response led to many observations of pharmacogenetic-based variations in pharmacokinetics. These and other discoveries and the subsequent ability to genotype led to the term pharmacogenetics. Today, as a consequence of sequencing and mapping of the human genome, pharmacogenetics is becoming the first drug discovery pipeline technology to affect the structure and economics of the pharmaceutical industry (Daly, 2010). During drug development, it is important to consider pharmacogenetic variation which could explain or even prevent discarding a drug candidate if appropriate genetic reasons are identified or when lack of response/occurrence of ADRs (adverse drug reactions) in drug therapy is experienced. Genetic variation is taken strongly into consideration also in clinic during individualized therapies. It helps to improve the number of responders and decrease the number of patients suffering from ADRs.