Friday, March 25, 2011

Genomics and Drug Response

Review Article

Genomic Medicine

W. Gregory Feero, M.D., Ph.D., Editor, Alan E. Guttmacher, M.D., Editor
Genomics and Drug Response

Liewei Wang, M.D., Ph.D., Howard L. McLeod, Pharm.D., and Richard M. Weinshilboum, M.D.

N Engl J Med 2011; 364:1144-1153March 24, 2011


Pharmacogenomics is the study of the role of inherited and acquired genetic variation in drug response.1 Clinically relevant pharmacogenetic examples, mainly involving drug metabolism, have been known for decades, but recently, the field of pharmacogenetics has evolved into “pharmacogenomics,” involving a shift from a focus on individual candidate genes to genomewide association studies. Such studies are based on a rapid scan of markers across the genome of persons affected by a particular disorder or drug-response phenotype and persons who are not affected, with tests for association that compare genetic variation in a case–control setting.2 An example is provided in this issue of the Journal: McCormack and colleagues, testing for genomewide association, identified an HLA allele that is associated with hypersensitivity reactions to the anticonvulsant and mood-stabilizing drug carbamazepine in persons of European descent.3 Pharmacogenomics facilitates the identification of biomarkers that can help physicians optimize drug selection, dose, and treatment duration and avert adverse drug reactions. In addition, pharmacogenomics can provide new insights into mechanisms of drug action and as a result can contribute to the development of new therapeutic agents.

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