Single gene behind 15 kinds of eczema

Irish researchers working in Dublin and Dundee have discovered 15 gene mutations that can lead to eczema, writes Dick Ahlstrom.

Better ways to diagnose and treat eczema should come from a collaboration between two Irish researchers working in Dublin and Scotland. They have discovered 15 different genetic causes for this common skin disorder and found that the form you get depends very much on the race into which you were born.

The work all comes down to a single gene, explains paediatric dermatologist at Our Lady's Hospital for Sick Children, Crumlin, Dr Alan Irvine.

"This new research now provides a target for direct intervention and the development of new therapeutic approaches," he says.

Dr Irvine, who is also in Trinity College Dublin's school of clinical medicine worked with Prof Irwin McLean of the University of Dundee to study in minute detail defects in the "filaggrin" gene that lead to eczema.

Both are graduates of Queen's University Belfast, with Irvine coming from Enniskillen and McLean from Ballymoney. They published their findings earlier this month in the prestigious journal, Nature Genetics.

The two have collaborated for the last 12 years on understanding the causes for this often seriously debilitating disorder. It affects one in five children here, with a similar incidence in most other countries, says Irvine.

Worse still, the appearance of eczema is often accompanied by the arrival of other inherited allergic disorders. "Eczema is not an isolated disease. Half of eczema patients also develop asthma and 70 per cent develop hay fever. The effects cluster together and they cluster in families," he explains.

The two devised a new method for analysing filaggrin in great detail, revealing all of the potential genetic errors seen in it that can lead to skin disorders.

The filaggrin gene produces a filament-like protein that binds with keratin fibres to hold the skin surface in place. Errors or mutations in the filaggrin gene are central to eczema and related conditions. These mutations either produce filaggrin that doesn't work properly, or totally block filaggrin production.

Their new study involved a genetic survey of Irish children, research funded by the Children's Medical Research Foundation of Our Lady's Hospital for Sick Children, Crumlin.

"It took 188 kids with eczema and studied their filaggrin gene in a really thorough way," Irvine says. The analysis delivered an overview of the types of mutations associated with the skin condition, providing a "genetic architecture" for the disease.

So far they have found 15 different mutations within the gene that result in eczema. If you have one of these, there is a 60 per cent chance of developing the disease and if two mutations are present in the filaggrin gene then you are almost certain to have the disease.

"It is a really strong predictor for whether you will get eczema," says Irvine.

There were five mutations most commonly seen, and the work showed that 9 per cent of the Irish population carried these gene defects.

Two other mutations were more likely to occur in Oriental populations and 4 per cent of that group carried these gene defects that could lead to eczema.

Very rare defects were also seen and these were associated with family gene inheritance.

Irvine and McLean's work on the filaggrin gene is important for many reasons. The fact that the presence of other allergic conditions such as asthma and hay fever can be linked to genetic mutations in a gene associated with skin is highly significant. "It provides a potential new paradigm for asthma," says Irvine.

It means that biochemists can study proteins associated with skin cells as an alternative to the assumption that allergic conditions must always be driven by errant immune cells.

The work also offers new approaches for treatment. "It does provide a target, he says. One option was to increase gene activity to deliver healthy filaggrin or block malfunctioning filaggrin.

It also provides more accurate diagnostic predictors for different manifestations of the disease, with a given mutation associated with one form of eczema and another genetic alteration linked to a different form.