Gen ontdekt die droge huid, eczeem en
astma veroorzaakt
Major gene discovered that causes dry
skin and leads to eczema and asthma
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.
This work was funded by The Wellcome
Trust and the skin disease charities DEBRA, PC Project, British Skin Foundation and
National Eczema Society. Biotechnology and Biological Sciences Research Council (award
D13460; C.N.A.P.), Scottish Enterprise Tayside and the Gannochy Trust (C.N.A.P. and S.M.).
C.N.A.P. is also supported by the Scottish Executive Genetic Health Initiative.
