title: Individualized risk for statin-induced myopathy: current knowledge, emerging challenges and potential solutions.
abstract: Skeletal muscle toxicity is the primary adverse effect of statins. In this review, we summarize current knowledge regarding the genetic and nongenetic determinants of risk for statin induced myopathy. Many genetic factors were initially identified through candidate gene association studies limited to pharmacokinetic (PK) targets. Through genome-wide association studies, it has become clear that SLCO1B1 is among the strongest PK predictors of myopathy risk. Genome-wide association studies have also expanded our understanding of pharmacodynamic candidate genes, including RYR2. It is anticipated that deep resequencing efforts will define new loci with rare variants that also contribute, and sophisticated computational approaches will be needed to characterize gene-gene and gene-environment interactions. Beyond environment, race is a critical covariate, and its influence is only partly explained by geographic differences in the frequency of known pharmacodynamic and PK variants. As such, admixture analyses will be essential for a full understanding of statin-induced myopathy.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Oates Institute for Experimental Therapeutics, Nashville, TN, USA.
authors.forename: QiPing
authors.initials: Q
authors.lastname: Feng
authors.forename: Russell A
authors.initials: RA
authors.lastname: Wilke
authors.forename: Tesfaye M
authors.initials: TM
authors.lastname: Baye
mesh_terms: D004843:Epistasis, Genetic; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D027381:Liver-Specific Organic Anion Transporter 1; D009135:Muscular Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D012306:Risk
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human