Identifying genetic risk factors for serious adverse drug reactions: Current progress and challenges

Russell A. Wilke, Debbie W. Lin, Dan M. Roden, Paul B. Watkins, David Flockhart, Issam Zineh, Kathleen M. Giacomini, Ronald M. Krauss

Research output: Contribution to journalArticle

250 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)904-916
Number of pages13
JournalNature Reviews Drug Discovery
Volume6
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Drug-Related Side Effects and Adverse Reactions
Chemical and Drug Induced Liver Injury
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Torsades de Pointes
Pharmaceutical Preparations
Pharmacokinetics
Alleles
Genotype
Morbidity
Mortality

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Wilke, R. A., Lin, D. W., Roden, D. M., Watkins, P. B., Flockhart, D., Zineh, I., ... Krauss, R. M. (2007). Identifying genetic risk factors for serious adverse drug reactions: Current progress and challenges. Nature Reviews Drug Discovery, 6(11), 904-916. https://doi.org/10.1038/nrd2423

Identifying genetic risk factors for serious adverse drug reactions : Current progress and challenges. / Wilke, Russell A.; Lin, Debbie W.; Roden, Dan M.; Watkins, Paul B.; Flockhart, David; Zineh, Issam; Giacomini, Kathleen M.; Krauss, Ronald M.

In: Nature Reviews Drug Discovery, Vol. 6, No. 11, 11.2007, p. 904-916.

Research output: Contribution to journalArticle

Wilke, RA, Lin, DW, Roden, DM, Watkins, PB, Flockhart, D, Zineh, I, Giacomini, KM & Krauss, RM 2007, 'Identifying genetic risk factors for serious adverse drug reactions: Current progress and challenges', Nature Reviews Drug Discovery, vol. 6, no. 11, pp. 904-916. https://doi.org/10.1038/nrd2423
Wilke, Russell A. ; Lin, Debbie W. ; Roden, Dan M. ; Watkins, Paul B. ; Flockhart, David ; Zineh, Issam ; Giacomini, Kathleen M. ; Krauss, Ronald M. / Identifying genetic risk factors for serious adverse drug reactions : Current progress and challenges. In: Nature Reviews Drug Discovery. 2007 ; Vol. 6, No. 11. pp. 904-916.
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