ArticlePharmacogenetics and genomics2011
Cerivastatin, genetic variants, and the risk of rhabdomyolysis.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 9 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 9 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- A systematic review and meta-analysis of genotype-based and individualized data analysis of SLCO1B1 gene and statin-induced myopathy.The pharmacogenomics journal · 2021 · on this mapPooled it
- Correlation between single-nucleotide polymorphisms and statin-induced myopathy: a mixed-effects model meta-analysis.European journal of clinical pharmacology · 2021Pooled it
- Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.Clinical pharmacology and therapeutics · 2019Pooled it
- Pharmacogenomics of statin-related myopathy: Meta-analysis of rare variants from whole-exome sequencing.PloS one · 2019Pooled it
- Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis.The pharmacogenomics journal · 2018Pooled it
- Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence.Cardiovascular research · 2018Pooled it
- Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case-Control Studies.Medicine · 2015Pooled it
- Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2014Pooled it
- SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.Clinical pharmacology and therapeutics · 2013Pooled it
- Phosphorylation of RYR1 at SerScience signaling · 2025Article
- Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.Genes · 2024Article
- Pharmacogenomic and Statistical Analysis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Pharmacogenetic Variation and Its Clinical Relevance in a Latin American Rural Population.International journal of molecular sciences · 2022Article
- Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy.International journal of molecular sciences · 2021Review
- Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies.International journal of molecular sciences · 2021Review
- Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy.Annals of medicine · 2020Review
- Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters.Pharmacogenomics · 2020Article
- Drug-drug-gene interactions and adverse drug reactions.The pharmacogenomics journal · 2020Review
- Pharmacogenetics of Statin-Induced Myotoxicity.Frontiers in genetics · 2020Review
Corrections and comments
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Authors and funding
21 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveThe withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis.
methodsThis study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association study to identify risk factors in other regions of the genome. A total of 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies.
resultsPermutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (P=0.002), but not variants in CYP2C8 (P=0.073) or UGTs (P=0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (P<0.001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P=1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (odds ratio: 0.48; 95% confidence interval: 0.36-0.63).
conclusionWe identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.