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A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

Title
 A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children
Authors
 Ji Hyun Lee; Kyung Won Kim; Myung Hyun Sohn; Min Goo Lee; Kyung Hwan Kim; Kyu-Earn Kim; Mi Na Kim; So Won Kim; Seung-Hyun Kim; Hae-Sim Park; Keun-Hwa Lee; Jaechun Lee; Heon Yung Gee
Issue Date
2011
Journal Title
 Journal of allergy and clinical immunology
ISSN
 0091-6749
Citation
 Journal of allergy and clinical immunology, Vol.128(6) : 1326-1334.e3., 2011
Abstract
BACKGROUND: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. OBJECTIVE: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. METHODS: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. RESULTS: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P = .004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. CONCLUSIONS: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94582
DOI
10.1016/j.jaci.2011.06.036
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
1. 연구논문 > 5. Research Institutes > 생체방어연구센터
1. 연구논문 > 1. College of Medicine > Dept. of Pediatrics
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S009167491101058X
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