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.

Author affiliations

1. Russell A. Wilke is at the Department of Medicine and Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
2. Debbie W. Lin and Kathleen M. Giacomini are at the Department of Biopharmaceutical Sciences, GD584 Rock Hall, 1550 4th Street, University of California, San Francisco, California 94143 USA.
3. Dan M. Roden is at Vanderbilt University School of Medicine, 2215B Garland Avenue, Nashville, Tennessee 37232-0575, USA.
4. Paul B. Watkins is at the Department of Medicine, General Clinical Research Center 3005 APCF, 101 Manning Drive, University of North Carolina Chapel Hill, North Carolina 27599, USA.
5. David Flockhart is at the Division of Clinical Pharmacology, Wishard Memorial Hospital Indiana, 1001 West 10^th Street, Indiana University School of Medicine, Indiana 46202, USA.
6. Issam Zineh is at the Departments of Pharmacy Practice and Pharmaceutics, College of Pharmacy; Division of Cardiovascular Medicine, College of Medicine; and Center for Pharmacogenomics, University of Florida, Gainesville, Florida 32610, USA.
7. These authors contributed equally to this work.
8. Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, California 94609; Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, California 94720; Department of Nutritional Sciences, University of California, Berkeley, California 94720, USA.

Correspondence to: Ronald M. Krauss^7,8 Email: rkrauss@chori.org

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