Pharmacogenomics of statins: understanding susceptibility to adverse effects.
Article Details
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Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA
Pharmacogenomics of statins: understanding susceptibility to adverse effects.
Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016.
- PubMed ID
- 27757045 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Lovastatin Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails Lovastatin Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Lovastatin Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails Lovastatin UDP-glucuronosyltransferase 1-1 Protein Humans NoSubstrateDetails Lovastatin UDP-glucuronosyltransferase 1-3 Protein Humans UnknownSubstrateDetails Lovastatin UDP-glucuronosyltransferase 2B7 Protein Humans UnknownSubstrateDetails Simvastatin Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails Simvastatin UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Simvastatin UDP-glucuronosyltransferase 1-3 Protein Humans UnknownSubstrateDetails Simvastatin UDP-glucuronosyltransferase 2B7 Protein Humans UnknownSubstrateDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Lovastatin Canalicular multispecific organic anion transporter 1 Protein Humans UnknownSubstrateDetails Lovastatin Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownNot Available Details Lovastatin Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownNot Available Details Simvastatin Canalicular multispecific organic anion transporter 1 Protein Humans UnknownSubstrateDetails Simvastatin P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Simvastatin Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorDetails Simvastatin Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownNot Available Details Simvastatin Solute carrier organic anion transporter family member 2B1 Protein Humans UnknownNot Available Details