LTC4-synthase A-444C polymorphism: lack of association with NSAID-induced isolated periorbital angioedema in a Spanish population.

BACKGROUND

The mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced reactions is unknown. However, strong evidence supports the hypothesis of an enhanced production of cysteinyl-leukotrienes. The existence of a polymorphism (A-444C) in the promoter region of the leukotriene (LT)C4-synthase gene (the terminal enzyme in the LTC4 production pathway) has been reported. This polymorphism has yielded contradictory results on its association with aspirin-induced asthma.

OBJECTIVE

The present study was designed to investigate the possible genetic association of C(-444) allele and a specific clinical phenotype of NSAID sensitivity, the NSAID-induced isolated periorbital angioedema, via a case/control study.

METHODS

The polymorphism A-444C was analyzed in 58 patients with NSAID-induced periorbital angioedema and 61 control subjects, who had undergone single-blind, placebo-controlled oral challenge. Genotype was determined by polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

We have not found an association of C(-444), allele with NSAID-induced isolated periorbital angioedema.

CONCLUSIONS

Further studies are needed to determine whether polymorphisms in the LTC4-synthase gene or other leukotriene-forming enzymes are involved in the pathogenesis of the different subsets of NSAID sensitivity.