Polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein are associated with chronic spontaneous urticaria and urinary leukotriene E4.

The mechanisms of chronic spontaneous urticaria (CSU) continue to be unknown. Our working hypothesis is that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be involved in the pathways leading to CSU. We examined five candidate polymorphisms of cyclo-oxygenases 1 and 2 and of 5-lipo-oxygenase-activating protein in 109 controls and in 94 CSU patients from Northern Italy. We also examined the levels of urinary leukotriene E4 (LTE4) before and after challenge with ASA. A multiple regression model was found to show that COX-2 5'UTR T/G, COX-2 Exon 10 T/C, and FLAP -336 G/A polymorphisms were significantly associated with CSU, with the minor allele more represented in CSU group. Similar results were obtained as regards the specific association with ASA-tolerated CSU and ASA-exacerbated CSU. Evaluating a polygenic model, reflecting the sum of the concomitant alleles associated with CSU (i.e. COX-2 5'UTR G allele, COX-2 Exon 10 C allele, and FLAP -336 G/A allele), the proportion of CSU patients increased progressively with the increasing number of unfavourable alleles. Finally, in a linear regression model after adjustment for disease status COX-1 22 T carriership remained a significant predictor of post-challenge high urinary LTE4 levels. Our results support the hypothesis that polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein may be associated with CSU.