Pharmacogenomics of statins: understanding susceptibility to adverse effects.

Article Details

Citation

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
DrugEnzymeKindOrganismPharmacological ActionActions
LovastatinCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
LovastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
LovastatinCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
LovastatinUDP-glucuronosyltransferase 1-1ProteinHumans
No
Substrate
Details
LovastatinUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
LovastatinUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
SimvastatinCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
SimvastatinUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Details
SimvastatinUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
SimvastatinUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
LovastatinCanalicular multispecific organic anion transporter 1ProteinHumans
Unknown
Substrate
Details
LovastatinSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Not AvailableDetails
LovastatinSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Not AvailableDetails
SimvastatinCanalicular multispecific organic anion transporter 1ProteinHumans
Unknown
Substrate
Details
SimvastatinP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
SimvastatinSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Inhibitor
Details
SimvastatinSolute carrier organic anion transporter family member 1B3ProteinHumans
Unknown
Not AvailableDetails
SimvastatinSolute carrier organic anion transporter family member 2B1ProteinHumans
Unknown
Not AvailableDetails