A Role of the ABCC4 Gene Polymorphism in Airway Inflammation ofAsthmatics

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473972.do
DOI
10.1155/2017/3549375
Title
A Role of the ABCC4 Gene Polymorphism in Airway Inflammation ofAsthmatics
Description
This research was supported by the National Research Foundation of Korea(NRF) grant, funded by the Korean government (MSIP) (Grant no.2015R1C1A2A01053492) and the Korea Health Technology R&D Project throughthe Korea Health Industry Development Institute (KHIDI) grant, andfunded by the Ministry of Health and Welfare, Republic of Korea (Grantno. HI16C0992).
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 < 0 01 for each) compared with a construct containing the -1508A allele. A functional polymorphism in the ABCC4 promoter, -1508A> G, may increase extracellular 15-hydroxyeicosatetraenoic acid, sphingosine-1-phosphate, and periostin levels, contributing to airway inflammation in asthmatics.
provenance
Made available in Cube on 2018-09-28T10:33:49Z (GMT). No. of bitstreams: 0
language
English
author
Palikhe, Sailesh
Uuganbayar, Udval
Trinh, Hoang Kim Tu
Ban, Ga-Young
Yang, Eun-Mi
Park, Hae-Sim
Kim, Seung-Hyun
orcid
Park, Hae-Sim/0000-0003-2614-0303
accessioned
2018-09-28T10:33:49Z
available
2018-09-28T10:33:49Z
issued
2017
citation
MEDIATORS OF INFLAMMATION
issn
0962-9351
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473972.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274087
Jurisdiction
Rep.of Korea
Project Name
Research Center for Biomedical Sciences
rights
openAccess
type
article


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