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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


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin 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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