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Published on: April 4, 2018
SLCO1B1 variants and statin-induced myopathy--a genomewide study
Common variants in the SLCO1B1 gene significantly increase the risk of statin-induced myopathy. Genetic testing for these variants can help personalize statin therapy for safer and more effective cardiovascular event prevention.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Genetics
Background:
- Statin therapy effectively lowers low-density lipoprotein cholesterol (LDL-C), reducing cardiovascular events.
- Higher statin doses and certain drug interactions can increase the risk of myopathy, a rare side effect.
Purpose of the Study:
- To identify genetic factors associated with statin-induced myopathy.
- To explore the role of SLCO1B1 gene variants in statin-related adverse effects.
Main Methods:
- A genomewide association study (GWAS) was conducted on 85 subjects with myopathy and 90 controls, all receiving high-dose simvastatin.
- Fine-mapping and replication studies were performed in larger cohorts using different simvastatin dosages.
Main Results:
- A strong association was found between myopathy and the rs4363657 single-nucleotide polymorphism (SNP) in the SLCO1B1 gene.
- This SNP is in linkage disequilibrium with rs4149056, which is linked to statin metabolism and significantly increases myopathy risk (OR=4.5 per C allele).
- Over 60% of myopathy cases were attributed to the C variant of rs4149056, with the association replicated in a separate trial.
Conclusions:
- Common SLCO1B1 variants are strongly linked to increased risk of statin-induced myopathy.
- Genotyping these variants could enable safer and more effective personalized statin therapy.
- This approach may help maximize the cardiovascular benefits of statins while minimizing adverse effects.
Related Concept Videos
Single Nucleotide Polymorphisms-SNPs
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Principles of Pharmacogenetics: Types of Genetic Variants
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenomics: Identification of New Drug Targets

