Pharmacogenomics and adverse drug reactions: the case of statins

Expert Opin Pharmacother. 2011 Jul;12(10):1499-509. doi: 10.1517/14656566.2011.563734. Epub 2011 Mar 29.

Abstract

Introduction: The use of genomics to predict adverse drug reactions (ADRs) has been the subject of much research over the last decade. Concerns about the muscular safety of statins, a highly prescribed group of drugs, are partially related to their high exposure. Many studies have identified a variety of genetic markers related to statin-induced myopathy. However, only polymorphisms in the SLCO1B1 gene (which encodes the carrier responsible for the hepatic uptake of statins, which, in turn, contributes to the regulation of plasma levels of SLCO1B1) were strongly associated with statin-induced muscular adverse effects. These was found to be most prominent for simvastatin. The strength of these findings relies on the use of modern genetic approaches, such as well-designed, case-controlled and genome-wide association studies. Nevertheless, the clinical use of this information is far from known at present and needs to be evaluated.

Areas covered: The links between genetic polymorphisms (i.e., SLCO1B1 gene) and statin-induced muscle ADRs and the methodological issues involved in the establishment of such an association are explored.

Expert opinion: Despite there being a statin-gene association for myopathy, in the case of some statins the usefulness of this information still needs to be proven.

Publication types

  • Review

MeSH terms

  • Genetic Markers
  • Genome-Wide Association Study
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Liver / metabolism
  • Liver-Specific Organic Anion Transporter 1
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / genetics
  • Organic Anion Transporters / blood
  • Organic Anion Transporters / genetics
  • Pharmacogenetics*
  • Polymorphism, Genetic
  • Simvastatin / adverse effects

Substances

  • Genetic Markers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Simvastatin