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Alpha-T-catenin (CTNNA3) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genome-wide association analysis.

Authors
Kim, SH; Cho, BY; Park, CS; Shin, ES; Cho, EY; Yang, EM; Kim, CW; Hong, CS; Lee, JE; Park, HS
Citation
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 39(2):203-212, 2009
Journal Title
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN
0954-78941365-2222
Abstract
BACKGROUND: Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI-induced asthma is still unknown.



OBJECTIVE: The objective of the study was to identify susceptibility alleles associated with the TDI-induced asthma phenotype.



METHODS: We conducted a genome-wide association study in 84 patients with TDI-induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with TDI-induced asthma enrolled in this study.



RESULTS: Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha-T catenin) were significantly associated with the TDI-induced asthma phenotype (5.84 x 10(-6) for rs10762058, 1.41 x 10(-5) for rs7088181, 2.03 x 10(-5) for rs4378283). Carriers with the minor haplotype, HT2 [GG], of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC(20) methacholine level (P=0.041) and lower mRNA expression of CTNNA3 than non-carriers (P=0.040). A genetic polymorphism in the 3' downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI-induced asthma phenotype (P=0.015 in recessive analysis model) and the prevalence of serum-specific IgG to cytokeratin 19 (P=0.031).



CONCLUSION: These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI-induced asthma.
MeSH terms
AdultAsthma/chemically induced*Asthma/genetics*B-Lymphocytes/metabolismBronchial Provocation TestsCell Line, TransformedFemaleGene Expression/geneticsGene FrequencyGenetic Predisposition to Disease/geneticsGenome-Wide Association Study*GenotypeHumansImmunoglobulin E/bloodImmunoglobulin G/bloodImmunoglobulin G/immunologyKeratin-19/immunologyMaleMiddle AgedOccupational Diseases/geneticsOligonucleotide Array Sequence AnalysisPolymorphism, Single Nucleotide/genetics*Risk FactorsToluene 2,4-Diisocyanate/adverse effects*alpha Catenin/genetics*
DOI
10.1111/j.1365-2222.2008.03117.x
PMID
19187332
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Journal Papers > Research Organization > Regional Clinical Trial Center
AJOU Authors
김, 승현박, 해심
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