Mechanisms of statin-induced myalgia assessed by physiogenomic associations
Open accessAbstract
Objective We investigated genetic variants predictive of muscular side effects in patients treated with statins. We utilized a physiogenomic approach to prototype a multi-gene panel correlated with statin-induced myalgia.Background Statin-induced myalgia occurs in ∼10% of lipid clinic outpatients. Its clinical manifestation may depend in part upon gene variation from patient to patient.Methods We genotyped 793 patients (377 with myalgia and 416 without) undergoing statin therapy at four U.S. outpatient clinic sites to evaluate 31 candidate genes from the literature for their association with statin-induced common myalgia.Results Three previously hypothesized candidate genes were validated: COQ2 (rs4693570) encoding para-hydroxybenzoate-polyprenyltransferase, which participates in the biosynthesis of coenzyme Q10 (p<0.000041); ATP2B1 (rs17381194) which encodes a calcium transporting ATPase involved in calcium homeostasis (p<0.00079); and DMPK (rs672348) which encodes a protein kinase implicated in myotonic dystrophy (p<0.0016).Conclusions The candidate genes COQ2, ATP2B1, and DMPK, representing pathways involved in myocellular energy transfer, calcium homeostasis, and myotonic dystonia, respectively, were validated as markers for the common myalgia observed in patients receiving statin therapy. The three genes integrated into a physiogenomic predictive system could be relevant to myalgia diagnosis and prognosis in clinical practice.
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Other candidate genes for statin-induced myalgia have been identified, each with a plausible pathophysiological relationship to muscle metabolism, but without adequate evidence to support their clinical relevance.
“Other candidate genes for statin-induced myalgia have been identified,115 each with a plausible pathophysiological relationship to muscle metabolism, but without adequate evidence to support their clinical relevance.”
From Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management (2015) · cites this paper as [115]
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- Authors
- Ruaño, G., Windemuth, A., Wu, A. H. B., Kane, J. P., Malloy, M. J., Pullinger, C. R., Kocherla, M., Bogaard, K., Gordon, B. R., Holford, T. R., Gupta, A., Seip, R. L., & Thompson, P. D.
- Affiliations
- Hartford Hospital (US)
- San Francisco General Hospital (US)
- University of California, San Francisco (US)
- Genomas (United States) (US)
- The Rogosin Institute (US)
- Yale University (US)
- Corresponding author
- Ruaño, Gualberto
- ORCID
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 218
- Issue
- 2
- Pages
- 451-456
- ISSN
- 0021-9150 (ISSN-L)
- PMC
- PMC3224998
- OpenAlex
- W2038595470
- Cited by
- 66
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 8 · 2013: 4 · 2012: 3
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL081893)
- National Institute of General Medical Sciences (R44GM085201)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- statin-induced myalgia, statin adverse effects, genetic susceptibility, COQ2, ATP2B1, DMPK, coenzyme Q10 biosynthesis, calcium homeostasis, myotonic dystrophy, candidate gene association, pharmacogenetics, gene panel
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Cross-Sectional Studies, Female, Humans, Hyperlipidemias, Male, Middle Aged, Muscular Diseases, Pharmacogenetics, Genetic Variation, Models, Statistical, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dyslipidemias
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