Pharmacogenetics of statins therapy.
Cardiovascular disease has become the global leading cause of death worldwide, representing the most frequent cause of morbidity and mortality in the developed world. Statins, the most widely prescribed cholesterol-lowering drugs, are considered to be first-line therapeutics for the prevention of coronary heart disease and atherosclerosis. Meta-analyses from several primary and secondary intervention studies have clearly shown that cholesterol-lowering medication, significantly reduces cardiovascular events, mortality, and morbidity, but considerable interindividual variation exists in response to statin therapy. Pharmacogenomics can provide important insights into statins therapy through elucidation of the genetic (or genomic) contribution to variable response for these drugs. The search for genetic polymorphisms may enable us to identify novel determinants of drug responsiveness by means of the study of three candidate genes groups: (1) genes encoding proteins involved in metabolism or drug transport, or both, that influence drug pharmacokinetics; (2) genes encoding proteins involved in mechanism of action and/or metabolic pathways on which drugs operate (that influence pharmacodynamics); (3) genes encoding proteins involved in the underlying disease condition or intermediate phenotype. This review briefly summarizes the recent pharmacogenomic and pharmacogenetic patents and the potential contributions of genetic variations in candidate genes related to lipid and lipoprotein metabolism and statins efficacy.
Puccetti
Luca
L
Department of Clinical Medicine and Immunological Sciences, Section of Internal Medicine, University of Siena, Siena, Italy. puccetti@unisi.it
Acampa
Maurizio
M
Auteri
Alberto
A
D003327:Coronary Disease / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors