Genetic Identification of Individuals with Increased Risk of Developing Occupational Skin Diseases
Our understanding of the complex genetic susceptibility to occupational contact dermatitis (OCD) is still in the early stage. The search for candidate susceptibility genes focused mainly on proteins involved in skin barrier and immune response which have a key role in both irritant and allergic contact dermatitis (respectively, ICD and ACD). Furthermore, for ACD genetic variations in enzymes involved in metabolism of contact allergens have been investigated. Among skin barrier genes, loss-of-function mutations in the filaggrin gene (FLG) have been identified as a risk factor for irritant contact dermatitis (ICD); the risk-modifying effect of FLG mutations was stronger in the presence of atopic dermatitis. In ACD, the impact of FLG mutations was allergen specific and dependent on the outcome measure and the exposure pattern. Several studies reported association of genetic polymorphisms in the metabolizing enzymes N-acetyltransferase and glutathione S-transferase with ACD; however the results are so far inconclusive. Among inflammatory genes, there appears to be an effect of TNF gene polymorphisms on susceptibility to both irritant and allergic CD, suggesting that they share some common pathways.
At present, the predictive value of genetic markers for the appearance of OCD is too low for reasonable identification of susceptible individuals in occupational health practice.
Further well-designed studies in larger cohorts with a well-defined disease phenotype and external exposure in the control as well as in the case group are needed to confirm and extend our knowledge of the impact of genetic variations on the susceptibility to OCD.
KeywordsAllergic contact dermatitis Irritant contact dermatitis Genetic susceptibilty Occupational
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