Genetic variants of the arachidonic acid pathway in non-steroidal anti-inflammatory drug-induced acute urticaria
Article first published online: 26 NOV 2012
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 42, Issue 12, pages 1772–1781, December 2012
How to Cite
Cite this as: Clinical & Experimental Allergy 2012 (42) 1772–1781., , , , , , , , , , , , , , ,
- Issue published online: 26 NOV 2012
- Article first published online: 26 NOV 2012
- Accepted manuscript online: 27 JUL 2012 11:23PM EST
- Manuscript Accepted: 23 JUL 2012
- Manuscript Revised: 17 JUL 2012
- Manuscript Received: 10 APR 2012
- Spanish Ministry Fund for Health in Spain (FIS) network RIRAAF. Grant Numbers: RD07/0064, PI071220, PI10/01598, PS09/02419, PI081383
- Instituto de Salud Carlos III
- Gobierno de Canarias. Grant Number: EMER07/001
- drug allergy;
- mast cells;
- skin reactions
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.
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.
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.
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.