Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness.
BACKGROUND
5-Lipooxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) are known as key enzymes in cysteinyl-leukotriene (cys-LT) production, critical mediators in aspirin acetylsalicyclic acid (ASA)-intolerant asthma (AIA). To date, studies of the promoter region of ALOX5 gene has revealed the potential influence of a variable number of tandem repeats of a Sp1- and Egr1-binding motif, on the transcription rate.


METHODS
To understand the pathological process that arises from cys-LT overproduction in AIA, we genotyped ALOX5 Sp1 and ALOX5AP poly(A) repeat promoter polymorphism by fluorescent-based capillary electrophoresis in the Korean population.


RESULTS
No significant differences in allele and genotype frequencies of the ALOX5 and ALOX5AP promoter polymorphisms were observed between the three groups. However, there was a strong association of the ALOX5 Sp1 repeat polymorphism with airway hyperresponsiveness (AHR; PC20 methacholine); AIA patients carrying a mutant allele (n > 5 or n < 5 repeats) showed increased AHR compared to AIA patients with wild-type genotype (P=0.003).


CONCLUSIONS
Although the alleles of the ALOX5 and ALOX5AP promoter cannot be considered as a prominent risk factor in the development of AIA, the genetic variant of tandem repeat (GGGCGG; Sp1-binding motif) in ALOX5 promoter is associated with the severity of airway hyperresponsiveness in AIA patients.
Kim
S-H
SH
Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
Bae
J-S
JS
Suh
C-H
CH
Nahm
D-H
DH
Holloway
J W
JW
Park
H-S
HS
D058927:5-Lipoxygenase-Activating Proteins; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D020080:Tandem Repeat Sequences
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D001094:Arachidonate 5-Lipoxygenase; D001241:Aspirin