Gene–environment interactions in atopic dermatitis

Autor: Simon G. Danby, Yiannis Vasilopoulos, Simon J. Ward, Alice Macgowan, Michael J. Cork, Jibu Varghese, Gordon W. Duff, Manar Moustafa, Rachid Tazi-Ahnini
Rok vydání: 2008
Předmět:
Zdroj: Drug Discovery Today: Disease Mechanisms. 5:e11-e31
ISSN: 1740-6765
DOI: 10.1016/j.ddmec.2008.02.003
Popis: Atopic dermatitis (AD) is a multifactorial, heterogeneous, disease that arises as a consequence of the interaction between genetic and environmental factors. Genetic variants found within several groups of genes have been associated with the development of a defective skin barrier including protease, protease inhibitor and structural genes. Loss-of-function mutations affecting the structural protein filaggrin in particular are a high risk factor for predisposing to AD. One common consequence expected of these ‘genetic factors’ is an increase in protease activity and decreased synthesis of lipid lamellae, leading to skin barrier breakdown. The use of soap and other detergents enhances this by raising stratum corneum pH, resulting in the inhibition of lipid biosynthesis and the activation of degradatory proteases. Exogenous proteases from sources including Staphylococcus aureus and house dust mite also contribute to degradation of the barrier. The combination of these environmental factors with genetic factors appears to result in varying degrees of skin barrier breakdown, which is dependent on the ‘dosage’ of each. Ultimately the breakdown of the skin barrier can permit the penetration of allergens, with subsequent T H 1 to T H 2 switching, the first step along the so-called atopic march. The interaction between genetic and environment factors can therefore be considered the initial event in the development of AD. Understanding these gene-environment interactions should lead to the better use of some topical products, avoidance of others, and the future development of products that can repair the skin barrier.
Databáze: OpenAIRE
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