{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:58:04Z","timestamp":1781200684884,"version":"3.54.1"},"reference-count":92,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01540"],"award-info":[{"award-number":["PI20\/01540"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/01566"],"award-info":[{"award-number":["PI23\/01566"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thematic Co-operative Centres: Inflammatory Diseases Network","award":["RICORS"],"award-info":[{"award-number":["RICORS"]}]},{"name":"Thematic Co-operative Centres: Inflammatory Diseases Network","award":["RD21\/0002\/0008"],"award-info":[{"award-number":["RD21\/0002\/0008"]}]},{"name":"Thematic Co-operative Centres: Inflammatory Diseases Network","award":["RD24\/0007\/0024"],"award-info":[{"award-number":["RD24\/0007\/0024"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"PhD student grants","doi-asserted-by":"publisher","award":["FI21\/00274"],"award-info":[{"award-number":["FI21\/00274"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"PhD student grants","doi-asserted-by":"publisher","award":["FI24\/00145"],"award-info":[{"award-number":["FI24\/00145"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rio Hortega Program","award":["CM223\/00151"],"award-info":[{"award-number":["CM223\/00151"]}]},{"name":"Miguel Servet II Program","award":["CPII19\/00006"],"award-info":[{"award-number":["CPII19\/00006"]}]},{"name":"Nicol\u00e1s Monardes Program","award":["C1-0006-2022"],"award-info":[{"award-number":["C1-0006-2022"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most consumed drugs worldwide and the main cause of drug hypersensitivity reactions (HSRs). The most common NSAID-HSR class is cross-hypersensitivity (CR), with patients reacting to NSAIDs from different chemical groups without specific immunological recognition, with NSAID-induced acute urticaria\/angioedema (NIUA) being the most frequent clinical phenotype. Although CR-HSRs are triggered by arachidonic acid (AA) alterations following cyclooxygenase (COX)-1 inhibition and cysteinyl-leukotrienes synthesis by 5-lypoxygenase (5-LO), current evidence supports the participation of additional mechanisms. As COX-1 and 5-LO head oxidative pathways, it is conceivable that enzymes participating in antioxidant control are involved in these mechanisms. In addition, as the CR-HSR susceptibility seems to be influenced by genetic factors, the possibility of genetic variants playing a role in such enzymes should not be excluded. Methods: In this observational case\u2013control study, we analysed for the first time in NIUA the overall genetic variability in key antioxidant defence enzymes genes, including catalase (CAT), glutathione peroxidase (GPX)-1 and 3, and superoxide dismutase (SOD)-1. We selected a set of tagging single nucleotide polymorphisms (tSNPs) in these genes using data from Europeans in the 1000 Genomes Project. Two independent Spanish populations (discovery and replication) of NIUA patients and NSAID-tolerant individuals were included. Results: Twenty-six tSNPs were genotyped in the discovery population, with three that were significantly associated with NIUA: rs3448 (GPX-1), rs3792798 (GPX-3), and rs10432782 (SOD-1). They were then genotyped in the replication group, with rs3792798 being protective and rs10432782 being associated with an increased NIUA risk. Conclusions: Our results suggest that a role for antioxidant enzyme polymorphisms in NIUA is required. Nevertheless, further research is needed to replicate our findings in other populations and their meaning at the molecular level and to investigate the role of such variants in other CR-HSR-induced phenotypes.<\/jats:p>","DOI":"10.3390\/ph19040522","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:02:49Z","timestamp":1774339369000},"page":"522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antioxidant Enzymes Genetic Variants Associated with Urticaria\/Angioedema Induced by Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs"],"prefix":"10.3390","volume":"19","author":[{"given":"Isabel M.","family":"Jim\u00e9nez-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Jurado-Escobar","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7784-4641","authenticated-orcid":false,"given":"Jos\u00e9","family":"Triano-Cornejo","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, Faculty of Medicine, University of Malaga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-7217","authenticated-orcid":false,"given":"Roc\u00edo","family":"S\u00e1enz de Santa Mar\u00eda","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"},{"name":"Allergy Unit, Malaga Regional University Hospital, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-1881","authenticated-orcid":false,"given":"Rafael","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane","family":"Allali-Bouamara","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0793-0168","authenticated-orcid":false,"given":"Victoria","family":"Raya-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Chac\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda y Alergia-Fundaci\u00f3n para la Gesti\u00f3n de la Investigaci\u00f3n en Salud de Sevilla, Unidad de Gesti\u00f3n Cl\u00ednica de Alergolog\u00eda, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"},{"name":"Departamento de Ciencias de la Salud y Biom\u00e9dicas, Universidad Loyola Andaluc\u00eda, 41704 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-8979","authenticated-orcid":false,"given":"Jos\u00e9 J.","family":"Laguna","sequence":"additional","affiliation":[{"name":"Allergy Unit, Cruz Roja Central Hospital, 28003 Madrid, Spain"},{"name":"Faculty of Medicine, Alfonso X El Sabio University, 28691 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Torres","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"},{"name":"Department of Medicine and Dermatology, Faculty of Medicine, University of Malaga, 29010 Malaga, Spain"},{"name":"Allergy Unit, Malaga Regional University Hospital, 29009 Malaga, Spain"},{"name":"Inflammatory Diseases Network (RICORS, RD24\/0007\/0024), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Centre for Nanomedicine and Biotechnology, IBIMA-Plataforma BIONAND, 29590 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Do\u00f1a","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"},{"name":"Allergy Unit, Malaga Regional University Hospital, 29009 Malaga, Spain"},{"name":"Inflammatory Diseases Network (RICORS, RD24\/0007\/0024), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-8735","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Cornejo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Allergy Research Group, IBIMA-Plataforma BIONAND, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga, 29009 Malaga, Spain"},{"name":"Allergy Unit, Malaga Regional University Hospital, 29009 Malaga, Spain"},{"name":"Inflammatory Diseases Network (RICORS, RD24\/0007\/0024), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"n104","DOI":"10.1136\/bmj.n104","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain","volume":"372","author":"Machado","year":"2021","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/pds.1592","article-title":"The pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) from 1997 to 2005: A nationwide study on 4.6 million people","volume":"17","author":"Fosbol","year":"2008","journal-title":"Pharmacoepidemiol. 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