title: Polymorphisms of cyclo-oxygenases and 5-lipo-oxygenase-activating protein are associated with chronic spontaneous urticaria and urinary leukotriene E4.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università di Palermo, Palermo, Italy. dilo601@unipa.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Pacor
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Florinda
authors.initials: F
authors.lastname: Listi
authors.forename: Vito
authors.initials: V
authors.lastname: Ditta
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Leto-Barone
authors.forename: Alberto
authors.initials: A
authors.lastname: D'Alcamo
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D014581:Urticaria / Q000235:genetics*; D055815:Young Adult
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; D017999:Leukotriene E4; D011451:Prostaglandin-Endoperoxide Synthases