CPIC Guideline for SLCO1B1, ABCG2, and CYP2C9 Genotypes Links Pharmacogenomics to Statin Safety
This CPIC guideline provides genotype-based therapeutic recommendations for all seven statins based on SLCO1B1, ABCG2, and CYP2C9 variants that alter systemic drug exposure and increase the risk of statin-associated musculoskeletal symptoms. Given that statins are among the most prescribed medications globally, pharmacogenomic testing can meaningfully improve adherence and long-term effectiveness. The guideline equips laboratories with clear genotype-to-phenotype mappings and prescribing implications for preemptive or reactive testing programs.
The original study
The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.
- Authors
- Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Practice Guideline
- PMID
- 35152405
Original abstract
Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy.