title: Genetic Predictors of Drug Hypersensitivity.
abstract: 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.
authors: Jose A
authors: JA
authors: Cornejo-Garcia
authors: Abderrahim
authors: A
authors: Oussalah
authors: Miguel
authors: M
authors: Blanca
authors: Rosa-Maria
authors: RM
authors: Gueant-Rodriguez
authors: Cristobalina
authors: C
authors: Mayorga
authors: Julie
authors: J
authors: Waton
authors: Annick
authors: A
authors: Barbaud
authors: Francesco
authors: F
authors: Gaeta
authors: Antonino
authors: A
authors: Romano
authors: Faculte de Medecine, Batiment C 2eme etage, 9 avenue de la Foret de Haye - B.P. 184, 54505 Vandoeuvre- les-Nancy CEDEX, France.
authors: Jean-Louis
authors: JL
authors: Gueant
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007073:Immunoglobulin E
keywords: Hypersensitivity; betalactams; candidate genes; genome-wide association study.; immediate and non-immediate reactions; nonsteroidal anti-inflammatory drugs; polymorphisms