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Update on the Genetic Basis of Drug Hypersensitivity Reactions

Jurado-Escobar R1*, Perkins JR1*, García-Martín E2, Isidoro-García M3,4,5, Doña I6, Torres MJ6, Cornejo-García JA1,6

*Both authors contributed equally to the manuscript.
1Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain
2Department of Pharmacology, University of Extremadura, Caceres, Spain
3Department of Clinical Biochemistry, Pharmacogenetics Unit, University Hospital of Salamanca, Salamanca, Spain
4Institute for Biomedical Research of Salamanca (IBSAL), Allergy Department, Salamanca, Spain
5Department of Medicine, Faculty of Medicine, University of Salamanca, Salamanca, Spain
6Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain

J Investig Allergol Clin Immunol 2017; Vol 27(6) : 336-345
doi: 10.18176/jiaci.0199

Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to β-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists.

Key words: Drug hypersensitivity, Immunologically-mediated reactions, Cross-hypersensitivity, Single-nucleotide polymorphisms, Genome-wide association study