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Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease

Authors
Song, YS; Yang, EM; Kim, SH; Jin, HJ; Park, HS
Citation
International archives of allergy and immunology, 159(2):157-161, 2012
Journal Title
International archives of allergy and immunology
ISSN
1018-24381423-0097
Abstract
Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome associated with chronic inflammation in the airways coincident with chronic rhinitis, sinusitis, recurrent polyposis and asthma. Eosinophils are the key inflammatory cells in the development of AERD. AERD has been attributed to abnormalities of the arachidonic acid metabolism, but the pathogenesis of AERD is not fully understood. Our aim was to investigate the genetic contribution of the arachidonate 15-lipoxygenase gene (ALOX15) to the development of AERD.



METHODS: We enrolled 171 patients with AERD, 229 patients with aspirin-tolerant asthma, and 195 normal healthy controls in a Korean population. Three polymorphisms (-427G/A, -272C/A, -217G/C) in the promoter region of ALOX15 were genotyped. The functional variability of the promoter polymorphisms were analyzed by luciferase reporter activity assay.



RESULT: No significant difference in the genotype frequency of the ALOX15 genetic polymorphism was found. Peripheral total eosinophil count was significantly higher in the patients carrying the GG genotype of the -427G/A polymorphism (p = 0.016). Similarly, the patients carrying haplotype 1 (ht1) (GCG) of -427G/A, -272C/A and -217G/C showed a significantly higher total eosinophil count compared to the other haplotypes (p = 0.008) in the AERD group. The promoter activity of the ht1 (GCG) construct was significantly higher compared to that of the ht3 (AGG) construct in A549 and U937 cells (both p < 0.001).



CONCLUSION: These results suggest that the promoter polymorphisms of the ALOX15 gene affect ALOX15 activity leading to increased eosinophil infiltration in AERD patients.
MeSH terms
AdultArachidonate 15-Lipoxygenase/*genetics/metabolismAspirin/*adverse effectsAsthma/enzymology/etiology/geneticsAsthma, Aspirin-Induced/enzymology/etiology/geneticsBase SequenceCase-Control StudiesDNA Primers/geneticsEosinophils/enzymology/immunologyFemaleGene FrequencyHaplotypesHumansLeukocyte CountMaleMiddle Aged*Polymorphism, Single NucleotidePromoter Regions, GeneticRepublic of KoreaRespiratory Hypersensitivity/*enzymology/etiology/*geneticsYoung Adult
DOI
10.1159/000335681
PMID
22652554
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현박, 해심
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