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Mediators of Inflammation
Volume 2017, Article ID 3549375, 7 pages
https://doi.org/10.1155/2017/3549375
Research Article

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

1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
2Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea
3Clinical Trial Center, Ajou University Medical Center, Suwon, Republic of Korea

Correspondence should be addressed to Hae-Sim Park; rk.ca.uoja@krapsh and Seung-Hyun Kim; rk.ca.uoja@hsmik

Received 14 March 2017; Accepted 10 April 2017; Published 4 June 2017

Academic Editor: Younghyo Kim

Copyright © 2017 Sailesh Palikhe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (, , , and , resp.) compared with noncarrier asthma patients. Luciferase activity was significantly enhanced in human epithelial A549 cells harboring a construct containing the −1508G allele ( 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.