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

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.