Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

BACKGROUND: The biological mechanisms by which cleaning products and disinfectants - an emerging risk factor - affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (GxE) may help identify new genes related to adult-onset asthma. OBJECTIVES: To identify interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress, and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma. METHODS: Data came from three large European cohorts: EGEA, SAPALDIA, and ECRHS. A candidate pathway-based strategy identified 163 genes involved in response to oxidative stress and potentially related with exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect GxE interactions, adjusted for age, sex and population ancestry in 2599 adults (Mean age: 47 years, 60% women, 36% exposed, 18% asthmatics). P-values were corrected for multiple comparisons. RESULTS: Ever exposure to LMW agents/irritants was associated with current adult-onset asthma (OR(95%CI)=1.28(1.04,1.58)). Eight SNP by exposure interactions at five loci were found at p