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Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness.

Kim, SH; Bae, JS; Suh, CH; Nahm, DH; Holloway, JW; Park, HS
Allergy, 60(6):760-765, 2005
Journal Title
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).

CONCLUSION: 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.
MeSH terms
5-Lipoxygenase-Activating ProteinsArachidonate 5-Lipoxygenase/genetics*Aspirin/adverse effects*Asthma/epidemiologyAsthma/genetics*Carrier Proteins/geneticsDrug Hypersensitivity/epidemiologyDrug Hypersensitivity/genetics*FemaleHumansKorea/epidemiologyMaleMembrane Proteins/geneticsPolymorphism, Genetic*Promoter Regions, GeneticTandem Repeat Sequences
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Rheumatology
AJOU Authors
김, 승현서, 창희남, 동호박, 해심
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