2026-06-14T05:06:35Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/170432024-11-28T15:20:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Agúndez, José A G author Ayuso, Pedro author Cornejo-García, José A author Blanca, Miguel author Torres, María J author Doña, Inmaculada author Salas, María author Blanca-López, Natalia author Canto, Gabriela author Rondon, Carmen author Campo, Paloma author Laguna, José J author Fernández, Javier author Martínez, Carmen author García-Martín, Elena author 2012-11-12 Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively).CONCLUSIONS AND IMPLICATIONS: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. 10.1371/journal.pone.0047571 1932-6203 PloS one http://hdl.handle.net/10668/1322 23152756 http://hdl.handle.net/20.500.12105/17043 Antiinflamatorios no esteroideos Hipersensibilidad medicamentosa Estudios de casos y controles Frecuencia de los Genes Polimorfismo de Nucleótido Simple iinmunoglobulina E The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.