Gene discovered that causes dry skin and leads to eczema and asthma

Mar 21 2006

Experts, lead by the University of Dundee, have discovered the gene which causes genetic skin conditions affecting millions of people.

Experts on genetic skin disorders at the University of Dundee, with collaborators in Dublin, Glasgow, Seattle and Copenhagen, have discovered the gene that causes dry, scaly skin and predisposes individuals to atopic dermatitis (eczema). Some of these individuals also develop a form of asthma that occurs in association with eczema. This work has been published in two consecutive papers in the March and April editions of the top genetics journal, Nature Genetics.

Currently, only symptomatic treatment of ichthyosis vulgaris and eczema is possible, using emollients and ointments to try to prevent the skin drying out or anti-inflammatory drugs to treat the inflamed skin in eczema. Now that the underlying gene defect behind this disorder is known, it will be possible to design new more effective therapies to tackle the root cause of the problem, rather than treating the symptoms. The Dundee group is already working on developing methods to treat and even prevent these diseases.

The gene in question produces a protein called filaggrin which is normally found in large quantities in the outermost layers of the skin. This protein is essential for skin barrier function, helping to form a protective layer at the surface of the skin that keeps water in and keeps foreign organisms out.

Reduction or complete absence of this important protein leads to impaired formation of the skin barrier. As a result, the skin dries out too easily and in addition, the outer layers of the skin are poorly formed and constantly flake off. As well as keeping water in, the skin barrier normally keeps foreign substances out of the skin. In people with filaggrin mutations, foreign substances can easily enter the skin and be seen by the immune system. This explains the development of inflamed skin (eczema). In some people, priming of the immune system through the "leaky" skin appears to lead to asthma when foreign substances later enter the lungs.

The first study, led by geneticists Professor Irwin McLean and Dr Frances Smith in Dundee and their dermatology colleague, Dr Alan Irvine, Our Lady's Hospital for Sick Children, Dublin, discovered that about 10% of European people carry a type of genetic mutation that switches off the filaggrin gene and this causes a very common dry, scaly skin condition, known as ichthyosis vulgaris. About 5 million people in the UK alone make only 50% of the normal amount of filaggrin protein and have a milder form of the disorder where the skin is dry and flaky. About 1 in 500 people, or 120,000 people in the UK, have both copies of the gene knocked out by genetic mutations and have no filaggrin protein whatsoever in the skin. These individuals have a severe and persistent form of the disease, often requiring specialist treatment.

A second study showed that many people with ichthyosis vulgaris also have eczema. Further research then showed a link between ichthyosis vulgaris, eczema and asthma. McLean, Smith and Irvine, in collaboration with Drs Colin Palmer and Somnath Mukhopadhyay of the Dundee BREATHE study, and Professor Hans Bisgaard in Copenhagen, showed in four independent experiments that these common mutations in the filaggrin gene are a major predisposing factor in the development of eczema and the form of asthma associated with eczema.

A significant association between filaggrin mutations and eczema was shown in familes affected by ichthyosis vulgaris.

About two-thirds of Irish children with eczema examined were found to carry one or more filaggrin mutations. In a study of Scottish children with asthma, there was a very strong association between filaggrin mutations in those children who had both eczema and asthma. In a study of Danish babies whose medical history was followed for the first years of life, there was again a strong association between filaggrin mutations and eczema. The Danish study also showed that more than 60% of the children carrying filaggrin mutations get eczema within the first couple of years of life.

About 5 million people in the UK carry one of the filaggrin mutations and consequently, have dry skin and are predisposed to eczema and to a lesser extent, asthma.

Worldwide, about 60 million people are estimated to carry these particular gene defects and more than 1 million are predicted to have the severe form of the disease as a consequence of these mutations alone.

The Dundee group already have evidence for the presence of different filaggrin mutations in other ethnic populations and it seems that reduction or absence of filaggrin in the skin is likely to be a major cause of dry skin and eczema worldwide.