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

Publication ,  Journal Article
Cooper-DeHoff, RM; Niemi, M; Ramsey, LB; Luzum, JA; Tarkiainen, EK; Straka, RJ; Gong, L; Tuteja, S; Wilke, RA; Wadelius, M; Larson, EA ...
Published in: Clin Pharmacol Ther
May 2022

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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Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

May 2022

Volume

111

Issue

5

Start / End Page

1007 / 1021

Location

United States

Related Subject Headings

  • Simvastatin
  • Rosuvastatin Calcium
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Neoplasm Proteins
  • Liver-Specific Organic Anion Transporter 1
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • Genotype
  • Cytochrome P-450 CYP2C9
 

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Cooper-DeHoff, R. M., Niemi, M., Ramsey, L. B., Luzum, J. A., Tarkiainen, E. K., Straka, R. J., … Voora, D. (2022). The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther, 111(5), 1007–1021. https://doi.org/10.1002/cpt.2557
Cooper-DeHoff, Rhonda M., Mikko Niemi, Laura B. Ramsey, Jasmine A. Luzum, E Katriina Tarkiainen, Robert J. Straka, Li Gong, et al. “The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.Clin Pharmacol Ther 111, no. 5 (May 2022): 1007–21. https://doi.org/10.1002/cpt.2557.
Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022 May;111(5):1007–21.
Cooper-DeHoff, Rhonda M., et al. “The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms.Clin Pharmacol Ther, vol. 111, no. 5, May 2022, pp. 1007–21. Pubmed, doi:10.1002/cpt.2557.
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. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022 May;111(5):1007–1021.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

May 2022

Volume

111

Issue

5

Start / End Page

1007 / 1021

Location

United States

Related Subject Headings

  • Simvastatin
  • Rosuvastatin Calcium
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Neoplasm Proteins
  • Liver-Specific Organic Anion Transporter 1
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Humans
  • Genotype
  • Cytochrome P-450 CYP2C9