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 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.


CONCLUSIONS
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.
Sánchez-Borges
M
M
Immunology and Allergology Service, El Avila Clinic and La Trinidad Medical Center, Caracas, Venezuela.
Acevedo
N
N
Vergara
C
C
Jiménez
S
S
Zabner-Oziel
P
P
Monzón
A
A
Caraballo
L
L
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000009:adverse effects* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012882:Skin Tests; D014581:Urticaria / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D007073:Immunoglobulin E; D004247:DNA; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D001241:Aspirin