Genetic Effect of ALOX15 Polymorphisms on Aspirin-Exacerbated Respiratory Disease

BACKGROUND AND OBJECTIVE: The 15(s)-hydroxyeicosatetraenoic acid (15(s)-HETE), a major metabolite of 15-lipoxygenase (15-LO) pathway, has been suggested to contribute to asthma pathogenesis. Elevated levels of 15(s)-HETE in bronchoalveolar lavage fluid (BALF) were demonstrated in severe asthmatics and aspirin-exacerbated respiratory disease (AERD). To investigate genetic contribution of ALOX15 in the development of AERD, we performed the genetic association of ALOX15 study in a Korean population. MATERIALS AND METHODS: One hundred-seventy one patients with AERD, 229 patients with aspirin-tolerant asthma (ATA), and 195 normal healthy controls (NC) were enrolled. Three polymorphisms (-427G/A, -272C/A, -217G/C) in the promoter were genotyped by a primer extension method. The functional variabilities of the promoter polymorphisms were analyzed by luciferase reporter activity assay, electrophoretic mobility shift assay (EMSA), and enzyme activity assay in red blood cell (RBC) lysates. RESULTS: No significant difference of the genotype frequency in ALOX15 genetic polymorphism was addressed. Peripheral blood total eosinophil count was significantly higher in AERD patients with the GG genotype of -427G>A polymorphism (P = 0.016) and ht1 [GCG] (P<0.001). The promoter activity of ht1 [GC] construct was significantly higher compared to that of ht3 [AG] construct in A549 and U937 cells (P<0.001, respectively). Moreover, -427 G specific binding protein was observed by EMSA. The AERD patients with the -427G allele had higher 15-LO activity and the metabolites of 15-LO in RBC lysates. CONCLUSION: These results suggest that the promoter polymorphisms of ALOX15 gene affect on 15-LO activity, finally leading to the development of AERD.

Author dc:creator

• 송, 영신

Contributors dc:contributor

• 박, 해심
• 대학원 의생명과학과
• 200924338

• 아스피린 과민성 천식
• 15-리폭시게나아제
• ALOX15
• Aspirin-Exacerbated Respiratory Disease

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000011377
000000011377

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/4347