title: A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children.
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.
authors.affiliation: Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Heon Yung
authors.initials: HY
authors.lastname: Gee
authors.forename: Jaechun
authors.initials: J
authors.lastname: Lee
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: So Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Kim
authors.forename: Kyu-Earn
authors.initials: KE
authors.lastname: Kim
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics; D007723:Korea; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D020871:RNA Stability; D060888:Real-Time Polymerase Chain Reaction; D044464:Receptor, PAR-2 / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D044464:Receptor, PAR-2; D007073:Immunoglobulin E