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Original Article


The A–444C Polymorphism in the Leukotriene C4 Synthase Gene Is Associated With Aspirin-Induced Urticaria


M Sánchez-Borges,1 N Acevedo,2,3 C Vergara,2,3 S Jiménez,2,3 P Zabner-Oziel,4 A Monzón,4 L Caraballo2,3

1 Immunology and Allergology Service, El Ávila Clinic and La Trinidad Medical Center, Caracas, Venezuela
2 Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
3 Fundemeb, Foundation for the Development of Medical and Biological Sciences, Colombia
4 Immunology Service, Institute of Oncology and Hematology, Ministry of Health and Social Development, Venezuela

J Investig Allergol Clin Immunol 2009; Vol. 19(5): 375-382



Background: Cysteinyl leukotriene production seems to be dysregulated in patients with hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). However, the underlying pathogenic mechanisms of these reactions are poorly understood. Previous studies have suggested a role for the A–444C polymorphism on the leukotriene C4 synthase gene (LTC4S) in aspirin-induced urticaria (AIU), but the results are controversial.

Objective: To evaluate in a case-control study whether the A–444C polymorphism in the promoter region of LTC4S is associated with AIU and atopic phenotypes in a Venezuelan population.

Methods: One hundred ten patients with AIU and 165 nonallergic controls were included. AIU was diagnosed by clinical history and confirmed by double-blind placebo-controlled oral provocation tests with NSAIDs. Genotyping of A–444C was performed by real-time
polymerase chain reaction using Taqman probes. Atopy was defined as a positive skin test result to any of the 25 aeroallergens tested.
Total and mite-specific immunoglobulin (Ig) E levels in serum were quantified using an enzyme-linked immunosorbent assay.

Results: A–444C was associated with AIU. The C allele was more frequent in patients with the cutaneous pattern of AIU and in patients with low skin reactivity to histamine. There was no association between A–444C and asthma, atopy, or total IgE levels.

Conclusion: The C allele of the A–444C polymorphism is a risk factor for AIU in our population and could be a genetic marker for this phenotype. Furthermore,
this single-nucleotide polymorphism is mainly associated with the cutaneous clinical pattern and with low skin response to histamine.

Key words: LTC4S. Histamine. Aspirin-induced urticaria. Leukotrienes. NSAIDs.