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

作者：Kim S H; Cho B Y; Park C S; Shin E S; Cho E Y; Yang E M; Kim C W; Hong C S; Lee J E; Park H S^*

来源：Clinical and Experimental Allergy, 2009, 39(2): 203-212.

DOI：10.1111/j.1365-2222.2008.03117.x

• asthma
• catenin
• genetic polymorphism
• genome-wide association study
• toluene diisocyanate

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 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.

• 出版日期2009-2