Genetic Predictors of Drug Hypersensitivity
2017
Our knowledge of genetic predisposing factors of drug hypersensitivity reactions
(DHRs) is still scarce. The analysis of the genetic basis of these reactions may contribute to
dissect the underlying mechanisms. We will outline current knowledge of the genetic predictors
of most common DHRs, including reactions to betalactam antibiotics (BLs), nonsteroidal
anti-inflammatory drugs (NSAIDs) and biological agents. The predictors of DHRs to
BLs are mostly linked to IgE-class switching, IgE pathway and atopy (IL4R, NOD2,
LGALS3) in replicated candidate gene studies, and to antigen presentation (HLA-DRA) in the
single replicated GWAS performed so far. The HLA-DRA variants are predictors of allergy
to penicillins, but not to cephalosporins and they influence also the sensitization against
prevalent allergens. The predictors of DHRs against NSAIDs are mostly linked to metabolism
of eicosanoids (ALOX5, ALOX5AP, TBXAS1, PTGDR, CYSLTR1). Single nucleotide
polymorphisms (SNPs) in genes involved in histamine biosynthesis and antigen presentation,
HLA, could also have a role in DHRs against NSAIDs. The intriguing association of DHRs to NSAIDs with
atopy should deserve further attention. Predictors of DHRs against asparaginase and other biological agents relate
to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively). The potential relationship of genetic predictors
of DHRs with pathomechanisms also involved in environmental exposure and atopy highlights the need to
perform GWAS in contrasted populations, taking into account world-wide variations of allele frequencies and
contrasted situations of environmental exposure.
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