Cytokine gene polymorphisms and susceptibility to chronic inflammatory diseases in occupational settings.
Toxicologist 2007 Mar; 96(1):443
There is a wide range of inter-individual variation in susceptibility to occupational and environmental related diseases. Mechanisms underlying susceptibility are largely unknown, but genetic predisposition is suspected to be a major factor. Recent evidence suggests that common polymorphisms in immune/inflammatory and antioxidant genes contribute to the pathogenesis of many complex human diseases. In light of this, functional variants of these genes have been examined for evidence of association with pulmonary fibrosis in a group of ex-coal miners, accelerated decline in lung function in firefighters and irritant contact dermatitis in healthcare workers. Several significant associations appeared between cytokine gene variants and disease progress and/or severity. The tumor necrosis factor-alpha (TNFá) -308, -238 and interleukin-1 receptor antagonist (IL-1RA) +2018 variants were found associated with the development and severity of silicosis. Also, associations between accelerated decline in lung function and genetic variations in several genes which regulate inflammation were found in firefighters that can not be explained by smoking history. Specifically, the presence of IL-1 RA +2018, TNFalpha - 238 and -308 variants were associated with the decline rate of lung function as measured by FEV1. Individual differences in response to common irritants (sodium dodecyl sulfate, benzalkonium chloride and sodium hydroxide) were investigated in a group of healthcare workers. Initial results confirmed interindividual variability in irritant susceptibility and provided base for investigating the role of genetic variations in response to irritants. In conclusion, the data suggest that genetic variations play a role in individual variability to certain occupational diseases. Such information can be used to help identify the most susceptible populations and apply relevant information to the risk assessment process by determining safe exposure levels for the most susceptible groups of workers.
Mathematical-models; Statistical-analysis; Genes; Genetic-factors; Genetics; Genotoxicity; Humans; Work-environment; Worker-health; Occupational-diseases; Occupational-hazards; Occupational-exposure; Occupational-respiratory-disease; Dermatitis; Risk-factors; Risk-analysis; Fire-fighters; Smoke-inhalation; Lung-irritants
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina