A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children - 30/11/11
, Kyung Won Kim, MD, PhD c, , Heon Yung Gee, MD, PhD a, Jaechun Lee, MD d, Keun-Hwa Lee, PhD d, Hae-Sim Park, MD, PhD e, Seung-Hyun Kim, PhD e, So Won Kim, MD a, Mi Na Kim c, Kyu-Earn Kim, MD, PhD c, Kyung Hwan Kim, MD, PhD a, Min Goo Lee, MD, PhD a, Myung Hyun Sohn, MD, PhD c, ⁎ 
Corresponding author: Myung Hyun Sohn, MD, PhD, Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, 134 Sinchon-Dong, Seoul 120-752, Korea.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.
Le texte complet de cet article est disponible en PDF.Key words : Protease-activated receptor-2, SNP, association study, atopy, mRNA stability
Abbreviations used : ECP, GADPH, PARs, SNP, TEC
Plan
| This study was supported by a faculty research grant of Yonsei University College of Medicine for 2010 (6-2010-0017), grants A030001 from the Korea Health 21 R&D Project, Environmental Health Center, Jeju, Korea, Ministry of Health & Welfare, Korea, and Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (2009-0075056 and 2011-0001173). |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 128 - N° 6
P. 1326 - décembre 2011 Retour au numéro
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