2026-04-29T12:23:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/178832024-02-10T20:01:45Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Amo, Gemma author Martí, Manuel author García-Menaya, Jesús M author Cordobés, Concepción author Cornejo-García, José A author Blanca-López, Natalia author Canto, Gabriela author Doña, Inmaculada author Blanca, Miguel author Torres, María José author Agúndez, José A G author García-Martín, Elena author 2019-06-25 The prevalence of allergic diseases and drug hypersensitivity reactions (DHRs) during recent years is increasing. Both, allergic diseases and DHRs seem to be related to an interplay between environmental factors and genetic susceptibility. In recent years, a large effort in the elucidation of the genetic mechanisms involved in these disorders has been made, mostly based on case-control studies, and typically focusing on isolated SNPs. These studies provide a limited amount of information, which now can be greatly expanded by the complete coverage that Next Generation Sequencing techniques offer. In this study, we analyzed the promoters of sixteen genes related to the Vitamin D pathway and the high-affinity IgE receptor, including FCER1A, MS4A2, FCER1G, VDR, GC, CYP2R1, CYP27A1, CYP27B1, CYP24A1, RXRA, RXRB, RXRG, IL4, IL4R, IL13, and IL13RA1. The study group was composed of patients with allergic rhinitis plus asthma (AR+A), patients with hypersensitivity to beta-lactams (BLs), to NSAIDs including selective hypersensitivity (SH) and cross-reactivity (CR), and healthy controls without antecedents of atopy or adverse drug reactions. We identified 148 gene variations, 43 of which were novel. Multinomial analyses revealed that three SNPs corresponding to the genes FCER1G (rs36233990 and rs2070901), and GC (rs3733359), displayed significant associations and, therefore, were selected for a combined dataset study in a cohort of 2,476 individuals. The strongest association was found with the promoter FCER1G rs36233990 SNP that alters a transcription factor binding site. This SNP was over-represented among AR+A patients and among patients with IgE-mediated diseases, as compared with control individuals or with the rest of patients in this study. Classification models based on the above-mentioned SNPs were able to predict correct clinical group allocations in patients with DHRs, and patients with IgE-mediated DHRs. Our findings reveal gene promoter SNPs that are significant predictors of drug hypersensitivity, thus reinforcing the hypothesis of a genetic predisposition for these diseases. 10.3389/fgene.2019.00582 1664-8021 Frontiers in genetics http://hdl.handle.net/10668/14234 31293618 http://hdl.handle.net/20.500.12105/17883 NSAIDs (non-steroidal anti-inflammatory drugs) Next-Generation Sequencing (NGS) Allergic rhinitis Asthma beta-lactam antibiotic Drugs hypersensitivity reactions High-affinity IgE receptor (FcεRI) Vitamin D Identification of Novel Biomarkers for Drug Hypersensitivity After Sequencing of the Promoter Area in 16 Genes of the Vitamin D Pathway and the High-Affinity IgE Receptor.