CTNNA3 (alpha-catenin) gene variants are associated with diisocyanate asthma in occupationally-exposed workers.
Yucesoy-B; Kashon-ML; Lummus-ZL; Johnson-VJ; Fluharty-KL; Gautrin-D; Malo-J; Cartier-A; Germolec-DR; Luster-MI; Bernstein-DI
Toxicologist 2013 Mar; 132(1):39
A genome-wide association study conducted recently in Korean subjects identified three CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs) (rs10762058, rs7088181, and rs4378283) associated with diisocyanate induced occupational asthma (DA). We conducted a candidate gene association study to replicate these findings in Caucasian workers. Genotyping was performed on genomic DNA, using a 5' nuclease PCR assay. Genotyping of these SNPs was performed in 410 diisocyanate-exposed and predominantly Canadian workers including: 132 workers with DA confirmed by a specific inhalation challenge (DA+); 131 symptomatic workers in whom DA was excluded by a negative challenge (DA-); and 147 HDI-exposed asymptomatic workers (AWs). CTNNA3 rs7088181 and rs10762058 SNPs were significantly associated with DA+ when compared to AWs (p.0.05) but not in comparison to DA- workers. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, minor allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA compared with AWs [OR= 9.05 (95% CI:1.69, 48.54) and OR = 6.82 (95% CI:1.65, 28.24), respectively]. In conclusion, we replicated association between two closely linked CTNNA3 gene SNPs and DA in Caucasian workers. These findings suggest that genetically altered expression of CTNNA3 might influence cellular adherence and epithelial barrier function in the airways and play a role in the pathogenesis of DA.
Toxicology; Genes; Gene-mutation; Genetic-factors; Genetics; Genotoxic-effects; Nucleotides; Isocyanates; Bronchial-asthma; Respiratory-system-disorders; Racial-factors; Deoxyribonucleic-acids; Nucleic-acids; Bioassays; Inhalants; Exposure-assessment; Employee-exposure; Occupational-exposure; Pathogenesis; Cell-alteration; Lung-cells; Cellular-reactions; Cellular-structures; DNA-damage
Healthcare and Social Assistance
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
University of Cincinnati