Rare variants in known and novel candidate genes predisposing to statin-associated myopathy

Pharmacogenomics. 2016 Aug;17(13):1405-14. doi: 10.2217/pgs-2016-0071. Epub 2016 Jun 14.


Aim: Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants.

Methods: We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis.

Results: In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20.

Conclusion: These findings support the role of rare variants and nominate loci for follow-up studies.

Keywords: CLCN1; atorvastatin; gene; myopathy; rosuvastatin; simvastatin; statin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chloride Channels / genetics
  • Exome / genetics
  • Female
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Male
  • Middle Aged
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / epidemiology
  • Muscular Diseases / genetics*
  • Rare Diseases / genetics


  • CLC-1 channel
  • Chloride Channels
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • SLCO1B1 protein, human