Please use this identifier to cite or link to this item: http://hdl.handle.net/10662/20140
Title: The Diamine Oxidase Gene Is Associated with Hypersensitivity Response to Non-Steroidal Anti- Inflammatory Drugs
Authors: García-Agúndez Pérez-Coca, José Augusto
Ayuso Parejo, Pedro
Cornejo García, José Antonio
Blanca Gómez, Miguel
Torres, María José
Doña, Inmaculada
Salas, María
Blanca López, Natalia
Canto Diez, María Gabriela
Rondón, Carmen
Campo Mozo, Paloma
Laguna Martínez, José Julio
Fernández, Javier
Martínez, Carmen
García Martín, Elena
Keywords: Diamino oxidasa;Diamine oxidase;Reacciones de hipersensibilidad;Hypersensitivity reactions;Antiinflamatorios no esteroideos;Non-steroidal antiinflammatory drugs
Issue Date: 2012
Abstract: 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.
URI: http://hdl.handle.net/10662/20140
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0047571
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DTMQU - Artículos

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