The Genetics of Statin-Induced Myopathy

Atherosclerosis. 2010 Jun;210(2):337-43. doi: 10.1016/j.atherosclerosis.2009.11.033. Epub 2009 Nov 27.

Abstract

Objective: Our goal was to use genetic variants to identify factors contributing to the muscular side effects of statins.

Background: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are usually well tolerated medications, but muscle symptoms, ranging from mild myalgia to clinically important rhabdomyolysis are an important side effect of these drugs and a leading cause of noncompliance. Recent results suggest that genetic factors increase the risk of statin-related muscle complaints. We performed a systematic review of the medical literature to determine genetic factors associated with statin myopathy.

Methods: We identified English language articles relating statin myopathy and genetic diseases and gene variants via a PubMed search. Articles pertinent to the topic were reviewed in detail.

Results/conclusions: Our review suggests that some patients are susceptible to statin myopathy because of pre-existing subclinical inherited muscular disorders, or genetic variation in statin uptake proteins encoded by SLCO1B1 or the cytochrome P enzyme system. Variations in genes affecting pain perception and polymorphism in vascular receptors may also contribute to statin myopathy. None of the variants identified in this review suggested novel metabolic mechanisms leading to statin myopathy.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Cytochrome P-450 Enzyme System / genetics
  • Female
  • Genetic Variation
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Middle Aged
  • Muscles / pathology
  • Muscular Diseases / chemically induced
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology*
  • Muscular Dystrophies / genetics
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Rhabdomyolysis / metabolism
  • Rhabdomyolysis / pathology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Cytochrome P-450 Enzyme System