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Genetic and Non-Genetic Determinants of the Pharmacological Activity of Statins

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Statins are cholesterol-lowering agents which belong to the group of the most commonly prescribed drugs. The use of statins has become the standard treatment in patients with an increased risk of cardiovascular and coronary heart diseases. However, many clinical studies have shown that 13 - 75% of patients fail to achieve LDL-cholesterol and total cholesterol target levels. The clinical implications of insufficient response include cardiovascular complications caused by atherosclerosis leading to acute myocardial infarction, stroke and death. The mechanism underlying statin resistance has been associated with genetic polymorphisms and nongenetic factors (e.g. concomitant diseases, drug-drug interactions, interactions with food and dietary supplements). The article provides a comprehensive update of the current knowledge regarding the role of genetic polymorphism and non-genetic determinants of cholesterol-lowering effect of statins. Dietary aspects of statin efficacy were also presented. The Pubmed search was performed to identify relevant papers from the last ten years which were included in the review. Consideration of the genetic and non-genetic determinants of pharmacological action of statins as well as mechanisms of drug-drug interactions may be useful in clinical practice for improving safety and efficacy of statin treatment.
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Keywords: CYP450 polymorphism; Cholesterol-lowering agents; dietary modulators; drug-drug interactions; pharmacogenetics; resistance to statin

Document Type: Research Article

Publication date: November 1, 2016

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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