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

Rhonda M. Cooper-DeHoff, Mikko Niemi, Laura B. Ramsey, Jasmine A. Luzum, E. Katriina Tarkiainen, Robert J. Straka, Li Gong, Sony Tuteja, Russell A. Wilke, Mia Wadelius, Eric A. Larson, Dan M. Roden, Teri E. Klein, Sook Wah Yee, Ronald M. Krauss, Richard M. Turner, Latha Palaniappan, Andrea Gaedigk, Kathleen M. Giacomini, Kelly E. CaudleDeepak Voora

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1007-1021
Number of pages15
JournalClinical pharmacology and therapeutics
Volume111
Issue number5
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
This work was funded by the National Institutes of Health (NIH) for CPIC (R24GM115264 and U24HG010135) and The Pharmacogenomics Knowledgebase (PharmGKB) (U24 HG010615). Additional author support includes P50GM115318 (R.M.K.), HL143161 (S.T.), U01HG007269 (R.M.C.‐D.), R01GM117163 (K.M.G., S.W.Y.), and K08HL146990 (J.A.L.). M.N. is funded by a European Research Council ERC Consolidator Grant (Grant agreement 725249).

Funding Information:
We acknowledge the critical input of Mary V. Relling (St Jude Children?s Research Hospital) and the members of the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Publisher Copyright:
© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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