Understanding the genetic causes of inter-patient variability. Clinical relevance with focus on cardiovascular drugs

Abstract

There is a large inter-patient variability concerning the response to drug therapy and a great interest for determining the causes of this variability. This review takes into discussion some aspects of cardiovascular drugs metabolism and transport, pointing out the effects of genetic variation. Isoenyzmes belonging to the Cytochrome P450 super family have an important role in cardiovascular drug metabolism, namely CYP 1A2; CYP 3A; CYP 2C19; CYP2C9; CYP 2D6, involved in the oxidative phase and also N-acetyltransferase 2, involved in the conjungative phase of the metabolism. P-glycoprotein is implied in cardiovascular drug transport. Polymorphisms of those enzymes and transport protein result in different phenotypes, that is the case of CYP isoenyzmes with abolished, low or increased activity and in the case of N-acetyltransferase 2, slow, intermediate and rapid acetylator phenotypes. There is hope that, in the future, a more individualized treatment of a certain disease, with minimum adverse effects and a maximum therapeutic effect, will be available, by means of genetic testing.