Identifying Genetic Risk Factors for Serious Adverse Drug Reactions: Current Progress and Challenges

Nat Rev Drug Discov. 2007 Nov;6(11):904-16. doi: 10.1038/nrd2423.

Abstract

Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury
  • Drug-Related Side Effects and Adverse Reactions*
  • Genetic Variation
  • Genomics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Liver Diseases / genetics
  • Long QT Syndrome / chemically induced
  • Long QT Syndrome / genetics
  • Muscular Diseases / chemically induced
  • Muscular Diseases / genetics
  • Pharmacogenetics*
  • Risk Factors
  • Torsades de Pointes / chemically induced
  • Torsades de Pointes / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors