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. Caudle; Deepak Voora

doi:10.1002/cpt.2557

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 journal › Article › peer-review

135 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 language	English (US)
Pages (from-to)	1007-1021
Number of pages	15
Journal	Clinical pharmacology and therapeutics
Volume	111
Issue number	5
DOIs	https://doi.org/10.1002/cpt.2557
State	Published - 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.

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Cooper-DeHoff, R. M., Niemi, M., Ramsey, L. B., Luzum, J. A., Tarkiainen, E. K., Straka, R. J., Gong, L., Tuteja, S., Wilke, R. A., Wadelius, M., Larson, E. A., Roden, D. M., Klein, T. E., Yee, S. W., Krauss, R. M., Turner, R. M., Palaniappan, L., Gaedigk, A., Giacomini, K. M., ... Voora, D. (2022). The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clinical pharmacology and therapeutics, 111(5), 1007-1021. https://doi.org/10.1002/cpt.2557

The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. / Cooper-DeHoff, Rhonda M.; Niemi, Mikko; Ramsey, Laura B. et al.
In: Clinical pharmacology and therapeutics, Vol. 111, No. 5, 05.2022, p. 1007-1021.

Research output: Contribution to journal › Article › peer-review

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 2022, 'The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms', Clinical pharmacology and therapeutics, vol. 111, no. 5, pp. 1007-1021. https://doi.org/10.1002/cpt.2557

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

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.",

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

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: {\textcopyright} 2022 The Authors. Clinical Pharmacology & Therapeutics {\textcopyright} 2022 American Society for Clinical Pharmacology and Therapeutics.",

year = "2022",

month = may,

doi = "10.1002/cpt.2557",

language = "English (US)",

volume = "111",

pages = "1007--1021",

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T1 - The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms

AU - Cooper-DeHoff, Rhonda M.

AU - Niemi, Mikko

AU - Ramsey, Laura B.

AU - Luzum, Jasmine A.

AU - Tarkiainen, E. Katriina

AU - Straka, Robert J.

AU - Gong, Li

AU - Tuteja, Sony

AU - Wilke, Russell A.

AU - Wadelius, Mia

AU - Larson, Eric A.

AU - Roden, Dan M.

AU - Klein, Teri E.

AU - Yee, Sook Wah

AU - Krauss, Ronald M.

AU - Turner, Richard M.

AU - Palaniappan, Latha

AU - Gaedigk, Andrea

AU - Giacomini, Kathleen M.

AU - Caudle, Kelly E.

AU - Voora, Deepak

N1 - 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.

PY - 2022/5

Y1 - 2022/5

N2 - 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.

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

Abstract

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