The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cooper-DeHoff, RM; Niemi, M; Ramsey, LB; Luzum, JA; Tarkiainen, EK; Straka, RJ; Gong, L; Tuteja, S; Wilke, RA; Wadelius, M; Larson, EA; Roden, DM; Klein, TE; Yee, SW; Krauss, RM; Turner, RM; Palaniappan, L; Gaedigk, A; Giacomini, KM; Caudle, KE; Voora, D

Published Date

  • May 2022

Published In

Volume / Issue

  • 111 / 5

Start / End Page

  • 1007 - 1021

PubMed ID

  • 35152405

Pubmed Central ID

  • PMC9035072

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1002/cpt.2557

Language

  • eng

Conference Location

  • United States