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Published on: April 1, 2019
The A-444C polymorphism in the leukotriene C4 synthase gene is associated with aspirin-induced urticaria
M Sánchez-Borges1, N Acevedo, C Vergara
1Immunology and Allergology Service, El Avila Clinic and La Trinidad Medical Center, Caracas, Venezuela.
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.
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