2026-04-29T04:52:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/170432024-11-28T15:20:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
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
authoraffiliation
[Agúndez,JAG; Martínez,C] Departamento de Farmacología, Universidad de Extremadura, Cáceres, Spain. [Ayuso,P; García-Martín,E] Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Cáceres, Spain. [Cornejo-García,JA] Laboratorio de Investigación, Fundación IMABIS, Málaga, Spain. [Blanca,M; Torres,MJ; Doña,I; Salas,M; Rondon,C; Campo,P] Servicio de Alergologia, Hospital Carlos Haya, Málaga, Spain. [Blanca-López,N; Canto,G; Servicio de Alergologia, Hospital Infanta Leonor, Madrid, Spain. [Laguna, JL] Servicio de Alergologia, Hospital Cruz Roja, Madrid, Spain. [Fernández,J] Servicio de Alergologia, Hospital San Juan, Alicante, Spain.
2024-01-15T18:16:53Z
2024-01-15T18:16:53Z
2012-11-12
http://hdl.handle.net/10668/1322
http://hdl.handle.net/20.500.12105/17043
23152756
10.1371/journal.pone.0047571
1932-6203
PloS one
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.
eng
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.
research article