6533b82afe1ef96bd128c490

RESEARCH PRODUCT

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

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description

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.