title: Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review.
abstract: Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure.
authors.affiliation: Faculty of Medicine of Nancy, NGERE - Nutrition, Genetics and Environmental Risk Exposure, INSERM U954, University of Lorraine, Vandoeuvre-lès-Nancy, France.|Department of Molecular Medicine and Personalized Therapeutics, Department of Biochemistry, Molecular Biology, Nutrition and Metabolism, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Oussalah
authors.affiliation: Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.|Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Mayorga
authors.affiliation: Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Department of Dermatology and Allergology, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Barbaud
authors.affiliation: Allergy and Immunology, Clinic Royal Liverpool and Broadgreen University Hospital, Thomas Drive Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Nakonechna
authors.affiliation: Immunoallergy Department, Centro Hospitalar Sao Joao, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Cernadas
authors.affiliation: Center for Allergy and Immunology Research, Tbilisi, Georgia.
authors.forename: M
authors.initials: M
authors.lastname: Gotua
authors.affiliation: Klinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, München, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brockow
authors.affiliation: Division of Paediatrics, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: J-C
authors.initials: JC
authors.lastname: Caubet
authors.affiliation: Dermatologie/Allergologie, Universitätsspital Basel, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Bircher
authors.affiliation: Department of Allergology and Pulmonology, University Children's Hospital, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Atanaskovic
authors.affiliation: Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Demoly
authors.affiliation: Hospital Sírio-Libanês, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: K Tanno
authors.affiliation: Academisch Medisch Centrum, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Terreehorst
authors.affiliation: Allergy Unit, Hospital de la Cruz Roja and Department of Immunology Alfonso X el Sabio University, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Laguna
authors.affiliation: Allergy Unit, Complesso Integrato Columbus, Rome and IRCCS Oasi Maria S.S., Troina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.affiliation: Faculty of Medicine of Nancy, NGERE - Nutrition, Genetics and Environmental Risk Exposure, INSERM U954, University of Lorraine, Vandoeuvre-lès-Nancy, France.|Department of Molecular Medicine and Personalized Therapeutics, Department of Biochemistry, Molecular Biology, Nutrition and Metabolism, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000209:etiology*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology* / Q000209:etiology*; D007073:Immunoglobulin E / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007073:Immunoglobulin E
keywords: IgE-mediated drug allergy; aspirin; beta-lactam antibiotics; genetic predictors; nonsteroidal anti-inflammatory drugs