Large Copy-Number Variations in Patients With Statin-Associated Myopathy Affecting Statin Myopathy-Related Loci
Open accessAbstract
Some patients are susceptible to statin-associated myopathy (SAM) either because of genetic variations affecting statin uptake and metabolism, or because they predispose their carriers to muscular diseases. Among the frequent variants examined using the genome-wide association study approach, SLCO1B1 c.521T>C represents the only validated predictor of SAM in patients treated with high-dose simvastatin. Our aim was to ascertain the overall contribution of large copy-number variations (CNVs) to SAM diagnosed in 86 patients. CNVs were detected by whole genome genotyping using Illumina HumanOmni2.5 Exome BeadChips. Exome sequence data were used for validation of CNVs in SAM-related loci. In addition, we performed a specific search for CNVs in the SLCO1B region detected recently in Rotor syndrome subjects. Rare deletions possibly contributing to genetic predisposition to SAM were found in two patients: one removed EYS associated previously with SAM, the other was present in LARGE associated with congenital muscular dystrophy. Another two patients carried deletions in CYP2C19, which may predispose to clopidogrel-statin interactions. We found no common large CNVs potentially associated with SAM and no CNVs in the SLCO1B locus. Our findings suggest that large CNVs do not play a substantial role in the etiology of SAM.
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Polymorphisms in the coenzyme Q2 gene, important in CoQ10 synthesis, are strongly associated with statin-induced myopathy.
“polymorphisms in the coenzyme Q2 gene, important in the synthesis of CoQ10, were reportedly strongly associated with statin‐induced myopathy.35, 36”
From Effects of Coenzyme Q10 on Statin‐Induced Myopathy: An Updated Meta‐Analysis of Randomized Controlled Trials (2018) · cites this paper as [35]
The Introduction says common genetic variations do not seem to be important determinants of statin-induced muscle toxicity, naming SLCO1B1 rs4149056 as the exception—not coenzyme Q2. It mentions COQ10A and COQ10B as genes affecting coenzyme Q10 production, but does not report a strong association between coenzyme Q2 polymorphisms and statin-induced myopathy. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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- Authors
- STRÁNECKÝ, V., NEŘOLDOVÁ, M., HODAŇOVÁ, K., HARTMANNOVÁ, H., PIHEROVÁ, L., ZEMÁNKOVÁ, P., PŘISTOUPILOVÁ, A., VRABLÍK, M., ADÁMKOVÁ, M., KMOCH, S., & JIRSA, M.
- Affiliations
- Charles University (CZ)
- Institute of Clinical and Experimental Medicine (CZ)
- ORCID
- Venue
- Physiological Research
- Published
- 2016-12-18
- Volume
- 65
- Issue
- 6
- Pages
- 1005-1011
- ISSN
- 0862-8408 (ISSN-L)
- 1802-9973
- OpenAlex
- W2519705412
- Cited by
- 7
- References
- 29
- Citations by year
- 2025: 1 · 2020: 1 · 2018: 3 · 2017: 2
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Physiological Research (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- 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 › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- statin-induced myopathy, copy number variation, SLCO1B1, simvastatin, genetic susceptibility, EYS, LARGE, CYP2C19, Rotor syndrome, congenital muscular dystrophy, statin metabolism
- MeSH terms
- Adult, Aged, Aged, 80 and over, Creatine Kinase, Female, Genotype, Heterozygote, Humans, Hyperbilirubinemia, Hereditary, Male, Middle Aged, Muscular Diseases, Genome, Human, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver-Specific Organic Anion Transporter 1, Genome-Wide Association Study, Genetic Loci, DNA Copy Number Variations, Cytochrome P-450 CYP2C19
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