What are the genetic changes related to atopic dermatitis ?
The genetics of atopic dermatitis are not completely understood. Studies suggest that several genes can be involved in development of the condition. The strongest association is with the FLG gene, which is mutated in 20 to 30 percent of people with atopic dermatitis compared with 8 to 10 percent of the general population without atopic dermatitis.  The FLG gene provides instructions for making a protein called profilaggrin, which is cut (cleaved) to produce multiple copies of the filaggrin protein. Filaggrin is involved in creating the structure of the outermost layer of skin, creating a strong barrier to keep in water and keep out foreign substances, including toxins, bacteria, and substances that can cause allergic reactions (allergens), such as pollen and dust. Further processing of the filaggrin protein produces other molecules that are part of the skin's "natural moisturizing factor," which helps maintain hydration of the outermost layer of skin.  Mutations in the FLG gene lead to production of an abnormally short profilaggrin molecule that cannot be cleaved to produce filaggrin proteins. The resulting shortage of filaggrin can impair the barrier function of the skin. In addition, a lack of natural moisturizing factor allows excess water loss through the skin, which can lead to dry skin.  Research shows that impairment of the skin's barrier function contributes to development of allergic disorders. An allergic reaction occurs when the body mistakenly recognizes a harmless substance, such as pollen, as a danger and stimulates an immune response to it. Research suggests that without a properly functioning barrier, allergens are able to get into the body through the skin. For unknown reasons, in susceptible individuals the body reacts as if the allergen is harmful and produces immune proteins called IgE antibodies specific to the allergen. Upon later encounters with the allergen, IgE antibodies recognize it, which stimulates an immune response, causing the symptoms of allergies, such as itchy, watery eyes or breathing difficulty. Although atopic dermatitis is not initially caused by an allergic reaction, flare-ups of the rashes can be triggered by allergens. The impaired barrier function caused by FLG gene mutations also contributes to the increased risk of asthma and other allergic disorders in people with atopic dermatitis.  Mutations in many other genes, most of which have not been identified, are likely associated with development of atopic dermatitis. Researchers suspect these genes are involved in the skin's barrier function or in the function of the immune system. However, not everyone with a mutation in FLG or another associated gene develops atopic dermatitis; exposure to certain environmental factors also contributes to the development of the disorder. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals.