期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 39, 期 2, 页码 203-212出版社
WILEY
DOI: 10.1111/j.1365-2222.2008.03117.x
关键词
asthma; catenin; genetic polymorphism; genome-wide association study; toluene diisocyanate
资金
- Korea Health 21 R&D Project of the Ministry of Health and Welfare, Republic of Korea [A030001, A050571]
- Korea Health Promotion Institute [A030001] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 PC20 methacholine level (P = 0.041) and lower mRNA expression of CTNNA3 than non-carriers (P = 0.040). A genetic polymorphism in the 30 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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