Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

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#atp-binding-cassette-transporter-subfamily-b #atp-binding-cassette-transporter-subfamily-g-member-2 #atp-binding-cassette-transporters #amidinotransferases #cytochrome-p-450-enzyme-system

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

Canestaro et al., 2014 | Genet Med | Systematic Review

Citation

Canestaro William J, Austin Melissa A, Thummel Kenneth E. Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genet Med. 2014-Nov;16(11):810-9. doi:10.1038/gim.2014.41

Abstract

Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.

Key Findings

Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Amidinotransferases
  • Cytochrome P-450 Enzyme System
  • Dose-Response Relationship, Drug
  • Genetic Variation
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Muscular Diseases
  • Neoplasm Proteins
  • Organic Anion Transporters
  • Simvastatin

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Research Support, N.I.H., Extramural, Systematic Review
  • Vertical: creatine

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09