Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges.
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.
Wilke
Russell A
RA
Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Lin
Debbie W
DW
Roden
Dan M
DM
Watkins
Paul B
PB
Flockhart
David
D
Zineh
Issam
I
Giacomini
Kathleen M
KM
Krauss
Ronald M
RM
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D064420:Drug-Related Side Effects and Adverse Reactions; D014644:Genetic Variation; D023281:Genomics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D008107:Liver Diseases / Q000235:genetics; D008133:Long QT Syndrome / Q000139:chemically induced / Q000235:genetics; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics; D010597:Pharmacogenetics; D012307:Risk Factors; D016171:Torsades de Pointes / Q000139:chemically induced / Q000235:genetics
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors