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New findings back eczema gene link

The results of twenty studies that strongly back up a genetic breakthrough made by a University of Dundee scientist will be announced this week. In March this year, a group lead by Irwin McLean discovered a major gene (filaggrin) that causes atopic dermatitis (commonly known as 'eczema'), the most common skin disease in the developed world.

'It is tremendously gratifying that our discovery is being upheld by so many other groups around the world. This firmly establishes that a skin barrier defect underlies eczema and related conditions and importantly, sets the scene for the development of new and more effective treatments', said Professor McLean.

At a genetics meeting this week, Professor Richard Trembath, of King's College London, will report on the incredibly strong association of the filaggrin gene mutations they have found in the English population, in collaboration with the Dundee group. The data from the English study suggests that filaggrin mutations are carried by almost half of adults who have had severe eczema since childhood. This sheds light on the type of eczema conferred by this gene, that is to say, it may be appear early in childhood, is more severe, and may persist into adulthood.

At the same conference, Professor McLean will present a further study in the Irish population of early onset eczema. The McLean group have now identified further defects in the gene that are also present in the general population. About 48 per cent of Irish cases of moderate to severe eczema carry one of five known defects in the filaggrin gene.

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A major problem encountered in the study of common disorders with a genetic component, such as eczema, is that one laboratory finds an association of the gene with the disease in question but others fail to duplicate the result in other populations and/or using other genetics methods. Fortunately, the filaggrin gene story is turning out to be very different.

In the original report from the McLean group, there were already a number of duplicate studies in the Irish, Scottish and Danish populations. Since that time, the Dundee group, with their collaborator Dr Alan Irvine in Dublin, have reported further replication studies in the Irish and Southern German populations by a variety of methods. Two further independent papers from research groups in Germany have also been published, again confirming the role of this gene in eczema. These studies, in addition to those already published by the McLean/Irvine group and those emerging from other laboratories around the world, bring the total number of positive replications to about twenty and strongly establish filaggrin as an important gene in eczema and related allergic conditions, such as eczema-associated asthma.

The McLean laboratory, at the Human Genetics Unit, University of Dundee, discovered that up to 10 per cent of people in European populations carry mutations that essentially 'knock out' or 'switch off' the filaggrin gene.

This gene normally makes large amounts of filaggrin protein in the outermost layers of the epidermis. This protein is essential for maintaining skin barrier function that prevents the skin drying out and also prevents the entry of foreign substances into the body. The gene is also linked to a form of asthma that accompanies eczema in patients, as well as a number of other allergic symptoms, including eczema-associated hay fever.

Professor McLean and Professor Trembath with present their results at the annual meeting of the British Society of Human Genetics, being held at the University of York from 18-20th September.

Anna Day | alfa
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Further reports about: Filaggrin McLean Northern Irish eczema

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