Researchers Identify Genes Associated with Adult Onset Asthma by Occupational Exposure

A large international study successfully identified novel genes in low molecular weight (LMW) agents/ irritants like those found in cleaning products and disinfectants that could be connected to adult onset asthma by occupational exposure.

Researchers sought to evaluate the role that biological mechanisms played in adult onset asthma and respiratory health connected to environmental risk factors in the workplace.

The study population included 2,599 participants and was restricted to patients with adult-onset asthma (older than 16-years). Each patient was evaluated for his occupational exposure and genotyped — a selection of genes related to oxidative stress responses was made using the Gene Ontology database.

The researchers then identified pathways that contained the selected genes and created a subset of pathways correlated to occupational exposure.

The research team led by Marta Rava, PhD (photo), with the French National Institute of Health and Medical Research (INSERM), utilized data from three European cohorts: the Epidemiological Study on Genetics and Environment of Asthma (EGEA) cooperative group, Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS).

In recent years, studies have confirmed the role occupational exposures to chemicals, particularly LMW agents in cleaners, are significant factors in adult onset asthma. A previous report estimated that 15% of adult onset asthma could be attributed to occupational exposure to chemicals found in cleaners and disinfectants.

The experts outlined that these chemicals triggered oxidative stress, which leads to airway inflammation and asthma. The study pointed out that although research had been conducted to confirm the role LMW agents play in adult-onset asthma, little research had been done to identify those genes involved in the development of asthma after occupational exposure.

However, according to Rava, specific genes connected to airway inflammation are likely to be involved in the development, activity, and severity of asthma. “These factors act primarily through complex mechanisms that involve interactions with environmental factors genetic and environmental (G x E), and with other genes (GxG) via pathways and networks.”

The team used a candidate pathway-based strategy to identify 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. They integrated information on the “biological processes shared by genres, the canonical pathways to which genes belong, and the biological knowledge related to the environmental exposure under the study.”

According to the study results, “A positive and significant association was found between lifetime occupational exposure to LMW agents or irritants and current adult-onset asthma.” Rava explained that “NF-κB is a ubiquitous transcription factor that is involved in the mechanism whereby oxidants affect the pathophysiology of asthma" and that the genes identified activate NF-kB in response to oxidative stress conditions like those created via exposure to LWM agents.” However, the researchers acknowledged further investigation could reveal stronger links among asthma occurrence, genetic mechanisms, and environmental exposures.

The article, "Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies," was published in the February 2017 issue of Environmental Health Perspectives.

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