Pharmacogenomics of statin therapy: any new insights in efficacy or safety?

Curr Opin Lipidol. 2014 Dec;25(6):438-45. doi: 10.1097/MOL.0000000000000125.

Abstract

Purpose of review: To examine the current evidence concerning the effects of genetic variation on statin-related low-density lipoprotein cholesterol reductions, clinical efficacy, and adverse events and the relevance for patient care.

Recent findings: Recent years have seen the emergence of large-scale genetic experiments, including genome-wide association studies and candidate gene studies, exploring the impact of common genetic variation on patient response to statins. These studies have built on previous smaller scale evidence, providing improved statistical power and enhanced ability to explore the genome. Current evidence suggests that common genetic variants do not alter low-density lipoprotein cholesterol response by more than a few percent, or materially alter the effect of statin on vascular risk reduction, and therefore that patients benefit from statins independent of common genetic variation. However, knowledge of SLCO1B1 genotypes is believed to have clinical utility for predicting myopathy risk and ensuring that statins are prescribed as safely as possible. Furthermore, new hypothesis-generating studies, such as those associating GATM with myopathy risk, offer potential insights for the future.

Summary: Common genetic variation does not appear to be an important determinant of statin response, with the exception of SLCO1B1 and risk of myopathy. Future studies will help to determine the impact of low-frequency and rare genetic variation on statin response.

Publication types

  • Review

MeSH terms

  • Amidinotransferases / genetics
  • Cholesterol, LDL / antagonists & inhibitors
  • Cholesterol, LDL / blood
  • Clinical Trials as Topic
  • Genetic Variation*
  • Genome, Human
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hyperlipidemias / blood
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / genetics
  • Hypolipidemic Agents / administration & dosage*
  • Hypolipidemic Agents / adverse effects
  • Liver-Specific Organic Anion Transporter 1
  • Muscular Diseases / blood
  • Muscular Diseases / chemically induced
  • Muscular Diseases / genetics*
  • Organic Anion Transporters / genetics*
  • Pharmacogenetics
  • Risk Factors

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Amidinotransferases
  • glycine amidinotransferase