Jimenez-Sanchez, Isabel M. , Jurado-Escobar, Raquel , Triano-Cornejo, Jose , Saenz de Santa Maria, Rocio , Nunez, Rafael , Allali-Bouamara, Imane , Raya-Lopez, Victoria , CHACON FERNANDEZ, PEDRO JOSE, Laguna, Jose J. , Torres, Maria J. , Dona, Inmaculada , Cornejo-Garcia, Jose A.
No
Pharmaceuticals (Basel)
Article
Científica
1
1
24/03/2026
001749596000001
2-s2.0-105037032835
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-control 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.
nonsteroidal anti-inflammatory drugs; hypersensitivity; urticaria; antioxidant enzymes; polymorphisms