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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Abstract:

Summary 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 × 10−6 for rs10762058, 1.41 × 10−5 for rs7088181, 2.03 × 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 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.

Cite this as: S‐H. Kim, B‐Y. Cho, C‐S. Park, E‐S. Shin, E‐Y. Cho, E‐M. Yang, C‐W. Kim, C‐S. Hong, J‐E. Lee and H‐S. Park, Clinical and Experimental Allergy, 2009 (39) 203–212.

Keywords: asthma; catenin; genetic polymorphism; genome-wide association study; toluene diisocyanate

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2222.2008.03117.x

Affiliations: 1: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, 2: Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Bucheon, 3: DNA Link Inc., Seoul, 4: Department of Internal Medicine, Inha University College of Medicine, Incheon and 5: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Publication date: February 1, 2009

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