Pharmacogenomics: state of the research and perspectives in clinical application

Abstract.

The person-to-person variability of drug response is a major problem in clinical practice and in drug development. It can lead to therapeutic failure or adverse drug reactions (ADRs) in individuals or subpopulation of patients. In addition to the high occurence of ADRs and the associated morbidity and mortality, substantial costs are incurred. Potential risk factors for drug inefficacy or toxicity include drug-drug interactions, the patient's age, renal and liver functions or other disease factors, and lifestyle variables such as smoking and alcohol consumption. In addition, it has become clear in recent years that genetic factors may also significantly modify drug responses or increase the risk for ADRs. Genetic variations in genes (polymorphisms) for drug-metabolizing enzymes, drug receptors, and drug transporters have been associated with individual variability in the efficacy and toxicity of drugs. It is now widely accepted that migraine is a polygenic and multifactorial disorders, thus considered to be a genetic complex disease. Genetic studies on migraine suggested a role of CACNA1A and DRD2 genes as susceptibility genes in this disorder.