Pharmacogenomics of adverse drug reactions: implementing personalized medicine.

Published

Journal Article (Review)

Pharmacogenomics aims to investigate the genetic basis of inter-individual differences in drug responses, such as efficacy, dose requirements and adverse events. Research in pharmacogenomics has grown over the past decade, evolving from a candidate-gene approach to genome-wide association studies (GWASs). Genetic variants in genes coding for drug metabolism, drug transport and more recently human-leukocyte antigens (HLAs) have been linked to inter-individual differences in the risk of adverse drug reactions (ADRs). The tight association of specific HLA alleles with Stevens-Johnson syndrome, toxic epidermal necrolysis, drug hypersensitivity syndrome and drug-induced liver injury underscore the importance of HLA in the pathogenesis of these idiosyncratic drug hypersensitivity reactions. However, as with the search for the genetic basis for common diseases, pharmacogenomic research, including GWAS, has so far been a disappointment in discovering major gene variants responsible for the efficacy of drugs used to treat common diseases. This review focuses on the pharmacogenomics of ADRs, the underlying mechanisms and the potential use of genomic biomarkers in clinical practice for dose adjustment and the avoidance of drug toxicity. We also discuss obstacles to the implementation of pharmacogenomics and the direction of future translational research.

Full Text

Duke Authors

Cited Authors

  • Wei, C-Y; Lee, M-TM; Chen, Y-T

Published Date

  • October 15, 2012

Published In

Volume / Issue

  • 21 / R1

Start / End Page

  • R58 - R65

PubMed ID

  • 22907657

Pubmed Central ID

  • 22907657

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/dds341

Language

  • eng

Conference Location

  • England