What does this gene do?
The FLG gene provides instructions for making a large protein called profilaggrin.
This protein is found in the cells in the outermost layer of the skin and plays a key role in maintaining this effective skin barrier. Profilaggrin is cleaved to produce many copies called filaggrin protein, these are important in the structure of the epidermis. Hydration of the skin is maintained by molecules produced after furthering processing of filaggrin.
The function of the outermost layer of the skin is to provide a barrier,by protecting the body and reducing water loss. It provides protection against any foreign substance, including bacteria, toxins and allergens, like pollen and dust mites. Filaggrin plays an integral role as a protein in the skin’s barrier function. It forms a strong barrier by bringing together proteins, strengthening and flattening cells resulting in the creation of tight bundle structures. Additionally these molecules maintain and correct acidity of the skin, this is another crucial aspect of the protective barrier.
FLG variants are strongly linked with atopic dermatitis, the skin disorder also known as atopic eczema. It’s characterised by dry, itchy skin and red rashes. The 28-40% of the general population that have the FLG mutation, of those, 20-30% of people have atopic dermatitis. This is clear that having the variant increases risk of developing atopic dermatitis. Other genes and environmental factor contribute to atopic dermatitis and not all that have the FLG mutation develop the skin condition.
Those with two copies ie AA allele, are at increased risk of developing atopic dermatitis than those with only one A allele. Due to the lack of filaggrin it also results in reduced natural moisturising factor for the skin, and excess water is lost and causes dry skin. This impairment has also been associated with the development of allergic disorders. Individuals with the FLG gene variant that have atopic dermatitis are at increased risk for developing asthma.
Another skin condition related to FLG mutations is called ichthyosis vulgaris. It is characterised by dry, scaly skin, aggravated during winter when humidity in the air is low. Individuals can also have very prominent creases in palms of hands and soles of their feet.
When there is only one copy of the A allele, individuals may only experience seasonal symptom and generally mildly affected.
If homozygous AA allele presents with more severe symptoms all year round. The same mechanism where there is a lack of filaggrin proteins results in dry, scaly skin. Additional environmental factors also increase risk for this skin condition such as smoking.
FLG gene mutations also increase risk of hay fever, food allergies, skin sensitivity to nickel.