4.6 Article

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

期刊

CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 111, 期 5, 页码 1007-1021

出版社

WILEY
DOI: 10.1002/cpt.2557

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资金

  1. National Institutes of Health (NIH) [R24GM115264, U24HG010135]
  2. Pharmacogenomics Knowledgebase (PharmGKB) [U24 HG010615]
  3. European Research Council ERC Consolidator Grant [725249]
  4. [P50GM115318]
  5. [HL143161]
  6. [U01HG007269]
  7. [R01GM117163]
  8. [K08HL146990]
  9. European Research Council (ERC) [725249] Funding Source: European Research Council (ERC)

向作者/读者索取更多资源

Statins are commonly prescribed medications that reduce cholesterol and prevent cardiovascular disease. However, statin-associated musculoskeletal symptoms can affect patient adherence and long-term effectiveness. Genetic variations in SLCO1B1, ABCG2, and CYP2C9 genes have been identified to impact the metabolism and adverse events of statins. This study summarizes the literature supporting these associations and provides therapeutic recommendations based on genotypes to improve the safety, adherence, and effectiveness of statin therapy.
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.

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