The A-444C polymorphism in the leukotriene C₄ synthase gene is associated with aspirin-induced urticaria

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 confi rmed 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 defi ned 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.