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A Role of the ABCC4 Gene Polymorphism in Airway Inflammation of Asthmatics

Authors
Palikhe, S; Uuganbayar, U; Trinh, HKT; Ban, GY; Yang, EM; Park, HS; Kim, SH
Citation
Mediators of inflammation, 2017:3549375-3549375, 2017
Journal Title
Mediators of inflammation
ISSN
0962-93511466-1861
Abstract
The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between ABCC4 gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (-1508A>G and -642C>G) in the ABCC4 promoter were genotyped. The functional variability of the promoter polymorphisms was analyzed by luciferase reporter assay. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Serum and urinary eicosanoid metabolites, sphingosine-1-phosphate, were evaluated by quadrupole time-of-flight mass spectrometry. Asthma patients carrying the G allele at -1508A>G had significantly higher serum levels of periostin, myeloperoxidase, and urinary levels of 15-hydroxyeicosatetraenoic acid and sphingosine-1-phosphate (P = 0.016, P = 0.027, P = 0.032, and P = 0.010, resp.) compared with noncarrier asthma patients. Luciferase activity was significantly enhanced in human epithelial A549 cells harboring a construct containing the -1508G allele (P G, may increase extracellular 15-hydroxyeicosatetraenoic acid, sphingosine-1-phosphate, and periostin levels, contributing to airway inflammation in asthmatics.
MeSH terms
AdultAllelesAsthma/genetics*FemaleGene Frequency/geneticsGenetic Predisposition to Disease/geneticsGenotypeHaplotypes/geneticsHumansInflammation/geneticsMaleMiddle AgedMultidrug Resistance-Associated Proteins/genetics*Polymorphism, Single Nucleotide/geneticsPromoter Regions, Genetic/genetics
DOI
10.1155/2017/3549375
PMID
28659663
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
반, 가영박, 해심김, 승현
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