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Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug¿Induced Acute Urticaria/ Angioedema

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Jurado Escobar, Raquel & Doña, Inmaculada & Triano Cornejo, José & Perkins, James R. & Pérez Sánchez, Natalia & Testera Montes, Almudena & Labella, Marina & Bartra, Joan & Laguna, José J. & Estravís, Miguel & Agúndez, José A. G. & Torres, María J. & Cornejo García, José A. .Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug¿Induced Acute Urticaria/ Angioedema.

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Jurado Escobar, Raquel & Doña, Inmaculada & Triano Cornejo, José & Perkins, James R. & Pérez Sánchez, Natalia & Testera Montes, Almudena & Labella, Marina & Bartra, Joan & Laguna, José J. & Estravís, Miguel & Agúndez, José A. G. & Torres, María J. & Cornejo García, José A.. Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug¿Induced Acute Urticaria/ Angioedema.

https://hdl.handle.net/20.500.12080/24467
dc.contributor.author Jurado Escobar, Raquel
dc.contributor.author Doña, Inmaculada
dc.contributor.author Triano Cornejo, José
dc.contributor.author Perkins, James R.
dc.contributor.author Pérez Sánchez, Natalia
dc.contributor.author Testera Montes, Almudena
dc.contributor.author Labella, Marina
dc.contributor.author Bartra, Joan
dc.contributor.author Laguna, José J.
dc.contributor.author Estravís, Miguel
dc.contributor.author Agúndez, José A. G.
dc.contributor.author Torres, María J.
dc.contributor.author Cornejo García, José A.
dc.date.accessioned 2021-06-01T16:11:55Z
dc.date.available 2021-06-01T16:11:55Z
dc.date.created 2021-04-30
dc.identifier.uri https://hdl.handle.net/20.500.12080/24467
dc.description.abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity reactions, probably due to their high consumption worldwide. The most frequent type of NSAID hypersensitivity is NSAID cross-hypersensitivity, in which patients react to NSAIDs from different chemical groups in the absence of a specific immunological response. The underlying mechanism of NSAID cross-hypersensitivity has been linked to cyclooxygenase (COX)-1 inhibition causing an imbalance in the arachidonic acid pathway. Despite NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype, most studies have focused on NSAID-exacerbated respiratory disease. As NSAID cross-hypersensitivity reactions are idiosyncratic, only appearing in some subjects, it is believed that individual susceptibility is under the influence of genetic factors. Although associations with polymorphisms in genes from the AA pathway have been described, no previous study has evaluated the potential role of cytosolic phospholipase A2 (cPLA2) variants. This enzyme catalyzes the initial hydrolysis of membrane phospholipids to release AA, which can be subsequently metabolized into eicosanoids. Here, we analyzed for the first time the overall genetic variation in the cPLA2 gene (PLA2G4A) in NIUA patients. For this purpose, a set of tagging single nucleotide polymorphisms (tagSNPs) in PLA2G4A were selected using data from Europeans subjects in the 1,000 Genomes Project, and genotyped with the iPlex Sequenom MassArray technology. Two independent populations, each comprising NIUA patients and NSAIDtolerant controls, were recruited in Spain, for the purposes of discovery and replication, comprising a total of 1,128 individuals. Fifty-eight tagSNPs were successfully genotyped in the discovery cohort, of which four were significantly associated with NIUA after Bonferroni correction (rs2049963, rs2064471, rs12088010, and rs12746200). These polymorphisms were then genotyped in the replication cohort: rs2049963 was associated with increased risk for NIUA after Bonferroni correction under the dominant and additive models, whereas rs12088010 and rs12746200 were protective under these two inheritance models. Our results suggest a role for PLA2G4A polymorphisms in NIUA. However, further studies are required to replicate our findings, elucidate the mechanistic role, and evaluate the participation of PLA2G4A variants in other phenotypes induced by NSAID cross-hypersensitivity. Keywords: NSAID cross-hypersensitivity, urticaria/angioedema, cytosolic phospholipase A2, polymorphisms, arachidomic acid es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri N/A es_ES
dc.title Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug¿Induced Acute Urticaria/ Angioedema es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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