Pharmacogenetics: a molecular sophistication or a new clinical tool for cardiologists?
The study of genetic risk factors for multifactorial diseases is attracting increasing interest. In particular interest has been focused on the interaction between genetic polymorphisms and environmental factors in determining the risk of disease. Among environmental factors therapeutic approaches should be considered. Therapeutic responses to a given drug, failure of drug efficacy, interindividual variability in side effects and toxicity of drugs could be at least partially accounted for by genetic polymorphisms. This paper summarizes the presently available applications of genetic concepts to some drugs commonly used in patients with cardiovascular disease. Statins and probucol fail to lower cholesterol levels in carriers of specific polymorphisms. The progression of cardiovascular disease is decreased by pravastatin only when certain polymorphisms are present. Induction problems and bleeding complications of warfarin occur in subgroups of populations carrying specific genetic variants of key enzymes in the drug metabolism. A new interpretation of the results of a thrombosis prevention trial will be given in the light of a genetic approach to pharmacology; indeed, prevention and treatment of thrombotic disease could be better focused on the basis of this knowledge. Future clinical trials and cost-effectiveness evaluation of drugs should be conducted taking these gene-drug interactions into account.
Dirckx
C
C
Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro, CH, Italy.
Donati
M B
MB
Iacoviello
L
L
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases; D001779:Blood Coagulation Factors / Q000235:genetics; D002986:Clinical Trials as Topic; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D000960:Hypolipidemic Agents; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D039181:Steroid 16-alpha-Hydroxylase