Amo, GemmaCornejo-Garcia, Jose AGarcia-Menaya, Jesus MCordobes, ConcepcionTorres, M JEsguevillas, GaraMayorga, CristobalinaMartinez, CarmenBlanca-Lopez, NataliaCanto, GabrielaRamos, AlfonsoBlanca, MiguelAgundez, Jose A GGarcia-Martin, Elena2016-11-112016-11-112016-09-29Amo G, Cornejo-García JA, García-Menaya JM, Cordobes C, Torres MJ, Esguevillas G, et al. FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS. Front Pharmacol. 2016; 7:353http://hdl.handle.net/10668/2511The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity. From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA), propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone, or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837, and rs2251746; FCER1B rs1441586, rs569108, and rs512555; FCER1G rs11587213, rs2070901, and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742, and rs1049793 in the HDC, HNMT, and DAO genes. No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug, or clinical presentation) were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG) were strongly related (P < 0.001 and P = 0.005, respectively) with selective hypersensitivity to ibuprofen. With regard to patients with selective hypersensitivity to ASA, men were more prone to develop such a reaction than women (P = 0.011), and the detrimental DAO SNP rs10156191 in homozygosity increased the risk of developing such hypersensitivity (P = 0.039).enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/FcεRIHistamineNon-steroidal anti-inflammatory drugs (NSAIDS)Hypersensitivity drug reactionsBiomarkersAcetaminofénAntiinflamatorios no EsteroideosAspirinaDiclofenacoDipironaÁcido flufenámicoMarcadores genéticosMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Anilides::Acetanilides::AcetaminophenMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Peripheral Nervous System Agents::Sensory System Agents::Analgesics::Analgesics, Non-Narcotic::Anti-Inflammatory Agents, Non-SteroidalMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Benzoic Acids::Hydroxybenzoic Acids::Salicylic Acids::AspirinMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylacetates::DiclofenacMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoles::Pyrazolones::Aminopyrine::DipyroneMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Benzoic Acids::Aminobenzoic Acids::Anthranilic Acids::Fenamates::Flufenamic AcidMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Genetic MarkersMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::HistamineMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylpropionates::IbuprofenMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin EMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Indoles::IndomethacinMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Carbocyclic::Phenylpropionates::KetoprofenMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic ModelsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthalenes::Naphthaleneacetic Acids::NaproxenMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoles::Pyrazolones::Phenylbutazone::OxyphenbutazoneMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazines::PiroxicamMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::PyridinesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Fc::Receptors, IgEMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compoundsresearch article27746735open accessHistaminaIbuprofenoInmunoglobulina EIndometacinaCetoprofenoPiroxicamPolimorfismo de Nucleótido SimplePiridinasReceptores de IgESulfonas10.3389/fphar.2016.003531663-9812PMC5040715