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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.

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dc.contributor.authorKim, SH-
dc.contributor.authorCho, BY-
dc.contributor.authorPark, CS-
dc.contributor.authorShin, ES-
dc.contributor.authorCho, EY-
dc.contributor.authorYang, EM-
dc.contributor.authorKim, CW-
dc.contributor.authorHong, CS-
dc.contributor.authorLee, JE-
dc.contributor.authorPark, HS-
dc.date.accessioned2010-12-20T05:48:20Z-
dc.date.available2010-12-20T05:48:20Z-
dc.date.issued2009-
dc.identifier.issn0954-7894-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/703-
dc.description.abstractBACKGROUND: 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.
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dc.language.isoen-
dc.subject.MESHAdult-
dc.subject.MESHAsthma-
dc.subject.MESHB-Lymphocytes-
dc.subject.MESHBronchial Provocation Tests-
dc.subject.MESHCell Line, Transformed-
dc.subject.MESHFemale-
dc.subject.MESHGene Expression-
dc.subject.MESHGene Frequency-
dc.subject.MESHGenetic Predisposition to Disease-
dc.subject.MESHGenome-Wide Association Study-
dc.subject.MESHGenotype-
dc.subject.MESHHumans-
dc.subject.MESHImmunoglobulin E-
dc.subject.MESHImmunoglobulin G-
dc.subject.MESHKeratin-19-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHOccupational Diseases-
dc.subject.MESHOligonucleotide Array Sequence Analysis-
dc.subject.MESHPolymorphism, Single Nucleotide-
dc.subject.MESHRisk Factors-
dc.subject.MESHToluene 2,4-Diisocyanate-
dc.subject.MESHalpha Catenin-
dc.titleAlpha-T-catenin (CTNNA3) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genome-wide association analysis.-
dc.typeArticle-
dc.identifier.pmid19187332-
dc.identifier.urlhttp://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=2009&volume=39&issue=2&spage=203-
dc.contributor.affiliatedAuthor김, 승현-
dc.contributor.affiliatedAuthor박, 해심-
dc.type.localJournal Papers-
dc.identifier.doi10.1111/j.1365-2222.2008.03117.x-
dc.citation.titleClinical and experimental allergy-
dc.citation.volume39-
dc.citation.number2-
dc.citation.date2009-
dc.citation.startPage203-
dc.citation.endPage212-
dc.identifier.bibliographicCitationClinical and experimental allergy, 39(2). : 203-212, 2009-
dc.identifier.eissn1365-2222-
dc.relation.journalidJ009547894-
Appears in Collections:
Journal Papers > Hospital > Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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