Pharmacogenomics of Drug Allergy

Adverse drug reactions (ADRs) are associated with significant morbidity, mortality, and cost. The pharmacogenomics of ADRs may encompass "on-target" pharmacologically mediated reactions or "off-target" pharmacologic or immune-mediated ADRs. Immune-mediated ADRs may be associated with immunologic memory of varying duration or without immune memory yet exhibit an immunologic phenotype such as urticaria.On-target pharmacologic ADRs are those that typically develop in a concentration-dependent manner and therefore involve genes associated with drug disposition and/or a known pharmacodynamic target. Reactions with an off-target pharmacologic or immunologic component involve genes associated with diverse pharmacologic, innate, and adaptive immune system pathways. These reactions include non-IgE-mediated mast cell activation, aspirin-exacerbated respiratory disease, nonimmune drug-induced thrombocytopenia, and heparin-induced thrombocytopenia, and also those ADRs with known immunologic memory such as IgE-mediated reactions and T cell-mediated delayed drug reactions.The utility of pharmacogenomic screening is influenced by a variety of economic, genetic, and clinical factors, which determine the overall burden of a particular ADR. Regardless of whether genes associated with drug allergy syndromes translate directly into the clinic as preventive markers, they provide valuable insights into mechanisms and pathogenesis that may help identify future therapeutic targets and guide safer drug design and development.This chapter discusses specific examples of each ADR classification and the associated pharmacogenomic risk factors and will highlight examples where pharmacogenomic associations have been successfully implemented into personalized medicine programs, as well as opportunities for future translation.