Impact of genetic polymorphisms on the efficacy of HMG-CoA reductase inhibitors.
Although pharmacologic treatment for cholesterol reduction represents an advance in cardiovascular and atherosclerosis treatment, the benefits of such therapy are still limited because of interindividual variability in the response to these drugs. Disease severity, treatment adherence, physiologic conditions, biologic conditions, and the patient's genetic profile could be cited as important factors in the evaluation of interindividual variability. In regard to the latter consideration, three large groups of genes could be investigated: (i) genes that code for proteins involved in metabolism and/or drug transport, thereby influencing the pharmacokinetics of these compounds; (ii) genes that code for proteins involved in the mechanism of action and/or in the metabolic pathway of drug action, and which therefore influence pharmacodynamics; and (iii) genes that code for proteins involved in direct development of the disease or in intermediate phenotypes. In this review we discuss pharmacogenetic studies of the HMG-CoA reductase inhibitors (statins) and the implications of pharmacogenetic considerations for predicting treatment efficacy and reducing the adverse effects of these drugs. Once new studies have been performed and most of the genetic variability associated with drug action has been revealed, the great challenge will be to apply this knowledge in clinical medicine.
Genetics Department, Biosciences Institute, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. mara.hutz@ufrgs.br
Mara H
MH
Hutz
Marilu
M
Fiegenbaum
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors