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.
Torres-Galván
M J
MJ
Research Unit, Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Canary Islands, Spain. usu02@invest.hpino.rcanaria.es
Ortega
N
N
Sánchez-García
F
F
Blanco
C
C
Carrillo
T
T
Quiralte
J
J
D000293:Adolescent; D000328:Adult; D000799:Angioedema / Q000139:chemically induced* / Q000235:genetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009916:Orbital Diseases / Q000139:chemically induced* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D016037:Single-Blind Method; D013030:Spain
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase