Did you know genetics influence your risk of eczema?

Living with eczema - how to cope when the FLG gene fails you

It’s a warm day in the middle of July. Two young women sit at the waiting area of a prestigious law office in New York, hoping to be their newest recruit. Amanda is the first to be interviewed. In her blue suit that matches her keen eyes, she appears calm and collected. Her rival Christine was at the top of her class. She’s known for her quick wit and perseverance.

If they perform equally well in their interviews, can you predict which one of them will go home the winner? Would it help if you knew that Christine’s face looked red, blotchy and swollen since her eczema flared-up? None of us want to admit it, but everything else being equal, we all know that Amanda was probably the first pick. That’s the power of a first impression – easily set, impossible to change. It’s also the sad reality faced by many with a visible skin condition.

Eczema is a condition characterized by inflamed or irritated skin. It’s estimated to affect one out of every three adults in the US. The risk of developing red, itchy skin is largely inherited. Variation in one protein found in our skin, filaggrin, is strongly linked to eczema. DNA sequence changes in the FLG gene (encodes filaggrin), contribute to our genetic predisposition to eczema.

We often think of our skin in relation to beauty and forget that it also serves as a barrier against the environment, keeping out pollutants, irritants and allergens. The outermost layer of our skin is called the stratum corneum. It consists of 15 to 20 layers of flattened, dead cells. Two proteins, keratin and filaggrin, are responsible for establishing and maintaining the structure of this impenetrable layer of skin.

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Filaggrin assembles keratin filaments together, causing them to collapse down into several layers of skin. These layers are then glued together by proteins called transglutaminases, after which filaggrin is broken down and retained to provide our skin moisture. Filaggrin is therefore key to forming the protective and properly moisturized barrier of our skin. Without it, the loss of structure in the barrier layer would allow our skin to be easily penetrated by allergens, leading to an immune response. Eczema, characterized by inflammation of the skin, is exactly that – an immune response to environmental triggers. And this is why structural changes to the barrier layer and genetic defects in the FLG gene have been proposed as the cause of eczema.

Over 40 distinct genetic changes in the FLG gene have been identified to date. Each of these changes either reduce or completely abolish the production of filaggrin. Some of these gene variants are linked to eczema (also known as atopic dermatitis). Interestingly, these FLG mutations appear to be distinct between different populations. For example, two variants of FLG called S2889X and S3296S are found exclusively in people with Japanese ancestry, while two other variants, rs558269137 and rs61816761 are found in Europeans. Several additional variants (rs200519781, rs138726443, rs121909626, rs150597413, 3673delC, and rs397507563) have also linked to an increased predisposition to eczema.

In one study, people with variants of FLG that couldn’t make any filaggrin were at high risk for developing atopic dermatitis. Another study highlighted the fact that 27% of the patients with atopic eczema had one or more changes in the FLG gene. Also, patients with atopic dermatitis had lower levels of filaggrin in their skin. To date, FLG remains one of the genes with the strongest evidence for genetic predisposition to eczema.

Eczema is a common skin disorder that affects many children, and sometimes the problems continue into adulthood. The severity of symptoms, as well as the triggers of eczema vary from person to person. Knowing ones risk for developing eczema, especially in the case of an infant, is most definitely the best way to keep this skin condition under control.

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