RT Journal Article
T1 FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS.
A1 Amo, Gemma
A1 Cornejo-Garcia, Jose A
A1 Garcia-Menaya, Jesus M
A1 Cordobes, Concepcion
A1 Torres, M J
A1 Esguevillas, Gara
A1 Mayorga, Cristobalina
A1 Martinez, Carmen
A1 Blanca-Lopez, Natalia
A1 Canto, Gabriela
A1 Ramos, Alfonso
A1 Blanca, Miguel
A1 Agundez, Jose A G
A1 Garcia-Martin, Elena
K1 Fcε
K1 RI
K1 Histamine
K1 Non-steroidal anti-inflammatory drugs (NSAIDS)
K1 Hypersensitivity drug reactions
K1 Biomarkers
K1 Acetaminofén
K1 Antiinflamatorios no Esteroideos
K1 Aspirina
K1 Diclofenaco
K1 Dipirona
K1 Ácido flufenámico
K1 Marcadores genéticos
AB The 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).
PB Frontiers Research Foundation
YR 2016
FD 2016-09-29
LK http://hdl.handle.net/10668/2511
UL http://hdl.handle.net/10668/2511
LA en
NO Amo 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; 7:353
NO This study was financed by grants PI12/00241, PI12/00324, PI15/00303, RETICS RD12/0013/0002, and RETICS RD16/0006/0004 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain, and GR15026 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union.
DS RISalud
RD Apr 6, 2025