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Pharmacogenomics of statins: understanding susceptibility to adverse effects
Authors Kitzmiller JP, Mikulik EB, Dauki AM, Mukherjee C, Luzum JA
Received 13 June 2016
Accepted for publication 12 August 2016
Published 3 October 2016 Volume 2016:9 Pages 97—106
DOI https://doi.org/10.2147/PGPM.S86013
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Martin H. Bluth
Joseph P Kitzmiller,1 Eduard B Mikulik,1 Anees M Dauki,2 Chandrama Murkherjee,1 Jasmine A Luzum3
1Department of Biological Chemistry and Pharmacology, College of Medicine, 2College of Pharmacy, The Ohio State University, Columbus, OH, 3Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
Abstract: Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes), statin efficacy (eg, drug targets and pathways), and end-organ toxicity (eg, myopathy pathways) highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy.
Keywords: cholesterol, myopathy, lipids, muscle toxicity, pharmacokinetics, pharmacogenetics
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