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

Lee, JH; Kim, KW; Gee, HY; Lee, J; Lee, KH; Park, HS; Kim, SH; Kim, SW; Kim, MN; Kim, KE; Kim, KH; Lee, MG; Sohn, MH
The Journal of allergy and clinical immunology, 128(6):1326-1334.e3, 2011
Journal Title
The Journal of allergy and clinical immunology
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.
MeSH terms
Asian Continental Ancestry Group/geneticsBase SequenceBlotting, WesternCase-Control StudiesChildFemaleGene ExpressionGene Expression ProfilingGene Expression Regulation/*geneticsGenetic Predisposition to Disease/*geneticsGenome-Wide Association StudyGenotypeHumansHypersensitivity, Immediate/*geneticsImmunoglobulin E/blood/geneticsKoreaMaleMolecular Sequence DataPhenotypePolymorphism, Single NucleotideProtein Structure, SecondaryRNA StabilityReal-Time Polymerase Chain ReactionReceptor, PAR-2/chemistry/*geneticsReverse Transcriptase Polymerase Chain Reaction
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
박, 해심김, 승현
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