Genetic variants of the arachidonic acid pathway in non-steroidal anti-inflammatory drug-induced acute urticaria

摘要

Background: To date, genetic studies of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) have been carried out mainly in aspirin-induced asthma and to a lesser extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs. Objective: In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID-induced AU. Methods: Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross-intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays. Results: A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case-control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p-value ≤ 0.041). A follow-up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10-6≤meta-analysis p-value ≤ 0.003). Conclusions and Clinical Relevance: Genetic variants of the AA pathway may play an important role in NSAID-induced AU. These data may help understand the mechanism underlying this disease.