Pharmacogenetics: Towards personalized medicine

Abstract

For 50 years, pharmacogenetics has been studying the genetic basis for variability in drug response between individual patients, both with respect to drug toxicity and drug efficacy. Following the completion of The Human Genome Project about three years ago, and the development of technologies allowing rapid identification of polymorphic alleles using DNA chips, pharmacogenetics would soon allow the introduction of personalized medicine. For most medical disciplines, this would allow pharmacotherapy according to each patient's individual genetic data. This would allow a reduction in the rates of adverse drug reactions, currently responsible by American and European estimates for about 6% of new admissions to internal medicine wards, and causing more morbidity annually than road accidents or breast cancer. The purpose of this review is to delineate the principles of pharmacogenetics, focusing on the aspects closest to implementation in the clinic: the polymorphism of liver CYP450 metabolic enzymes, mostly CYP2D6 and CYP2C19. We shall also review current efforts to better understand the scope of human genome diversity, and present several examples for variability in drug efficacy and genetic polymorphism of drug target genes. Education of health professionals in pharmacogenetics as part of their pharmacology curricula, and explaining its potential to the general public, would be indispensable for the success of personalized medicine.