Association of genetic variations in antioxidant enzyme genes with diisocyanate-induced asthma in exposed workers.
Yucesoy-B; Johnson-VJ; Fluharty-K; Slaven-J; Lummus-ZL; Kissling-GE; Germolec-DR; Luster-MI; Bernstein-DI
Toxicologist 2011 Mar; 120(Suppl 2):293
Diisocyanates are the most common cause of occupational asthma induced by low molecular- weight agents. It has been shown that diisocyanates induce oxidative stress when they react with specific proteins in human airway epithelial cells and this process contributes to the pathogenesis of diisocyanate-induced asthma (DA). In this respect, variability in the antioxidant defenses may play a role in DA susceptibility. A case-control study was conducted to investigate whether genetic variations within antioxidant enzyme genes, glutathione S-transferases (GSTM1- GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (MnSOD) and microsomal epoxide hydrolase (EPHX1), play a role in susceptibility to DA. The study population consisted of 252 workers exposed to diisocyanates (hexamethylene diisocyanate, methylene diphenyl diisocyanate, and toluene diisocyanate) of which 102 were diagnosed with DA based on a positive specific inhalation challenge. Genotype analysis was performed on genomic DNA, using a 5' nuclease PCR assay. The EPHX1 SNP (rs2740171) and GSTT1 gene deletion were associated with altered risk of developing DA after adjusting for potential confounders. Since EPHX1 and GSTT1 genes are important components of lung defense against oxidative stress, variations in these genes which regulate their expression may represent important disease modifiers and contribute to DA susceptibility.
Allergic-reactions; Allergies; Biological-effects; Genetic-factors; Inhalation-studies; Lung-function; Lung-irritants; Molecular-biology; Molecular-structure; Oxidative-metabolism; Oxidative-processes; Oxidative-processes; Physiological-effects; Pulmonary-function; Pulmonary-system; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Risk-analysis; Risk-factors; Statistical-analysis; Tissue-disorders
Healthcare and Social Assistance; Services
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
University of Cincinnati