title: The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy.
abstract: Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non-synonymous coding single-nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly.
authors.affiliation: Oates Institute for Experimental Therapeutics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. russell.a.wilke@vanderbilt.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Wilke
authors.forename: L B
authors.initials: LB
authors.lastname: Ramsey
authors.forename: S G
authors.initials: SG
authors.lastname: Johnson
authors.forename: W D
authors.initials: WD
authors.lastname: Maxwell
authors.forename: H L
authors.initials: HL
authors.lastname: McLeod
authors.forename: D
authors.initials: D
authors.lastname: Voora
authors.forename: R M
authors.initials: RM
authors.lastname: Krauss
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.forename: R M
authors.initials: RM
authors.lastname: Cooper-Dehoff
authors.forename: L
authors.initials: L
authors.lastname: Gong
authors.forename: T E
authors.initials: TE
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Wadelius
authors.forename: M
authors.initials: M
authors.lastname: Niemi
mesh_terms: D011307:Drug Prescriptions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D027381:Liver-Specific Organic Anion Transporter 1; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D018570:Risk Assessment; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D019821:Simvastatin