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Gene region for atopic dermatitis discovered on chromosome 3

Atopic dermatitis is a common chronic inflammatory skin disease. Along with asthma and hay fever, atopic dermatitis is an important manifestation of atopy that is characterized by the tendency to form allergy antibodies (IgE) to environmental allergens.

Inherited and environmental factors determine the risk of developing atopic dermatitis. Researchers at the Charité Division of Pediatric Pneumology and Immunology of the Humboldt University of Berlin and the Max Delbrück Center for Molecular Medicine (MDC), Berlin Buch, have carried out a European multinational investigation and identified, for the first time, a region on chromosome 3 which contains a gene for atopic dermatitis. This research has just appeared in the latest issue of Nature Genetics (Vol. 26, No. 4, pp.470-473)* .

In industrialized countries, 10 - 15 per cent of children suffer from atopic dermatitis. The condition usually affects young infants and children and is commonly the first manifestation of allergy. ”Although atopic dermatitis usually gets better or even disappears as the child grows older, children with atopic dermatitis have a significantly increased risk of developing asthma or hay fever later on in life” says Dr. Young-Ae Lee, a pediatrician and researcher who works at the Charité and the Gene Mapping Center at the MDC.

The study just reported in Nature Genetics received financial support from the Federal German Research Ministry and the German Human Genome Project. Researchers from Germany, Italy, Sweden and the Netherlands investigated almost 200 families with over 800 family members over a three year period. Each of the investigated families had at least two children who had developed atopic dermatitis before they were two years of age. In this study, all the chromosomes were systematically screened with 400 genetic markers to identify chromosomal regions that were more frequently inherited by affected siblings than expected by chance alone. Such chromosomal regions are said to be linked with the disease. It was found that a region on chromosome 3 is linked to atopic dermatitis. The investigators conclude that this region contains a gene which predisposes to atopic dermatitis.

Significance of
atopic dermatitis for the development of allergies

Most children who suffer from atopic dermatitis produce ”allergy antibodies” (IgE) to food or environmental allergens. Three quarters of the 421 children with atopic dermatitis investigated in this study suffered from allergies. The investigators also looked for chromosomal regions that are linked to allergic sensitization. Interestingly, linkage of the same region on chromosome 3 with allergic sensitization was detected. This study also showed, that for allergic sensitization the parental origin of the disease allele is important. Inheritance from the mother appears to be very important for predisposition to allergy while inheritance from the father has little effect on the subsequent development of allergy. The next step in this research will be to identify the gene that predisposes to atopic dermatitis. ”We believe that the susceptibility to atopic dermatitis is based on changes in the disease gene. If we can find out the mechanism of how this gene causes atopic dermatitis and allergies, then we should be able to develop targeted treatment strategies in the future”.

*A major susceptibility locus for atopic dermatitis maps to chromosome 3q21

1,2 Young-Ae Lee, Ulrich Wahn, 2 Rainer Kehrt, 3 Luigi Tarani, Luisa Businco, 4 Dan Gustafsson, 4 Florence Andersson, Arnold P. Oranje, 5 Albert Wolkertstorfer, 6 Andrea v. Berg, 7 Ute Hoffmann, 8 Wolfgang Küster, Thomas Wienker, 1,9 Franz Rüschendorf, 1 André Reis

1Max-Delbrück-Centre (MDC) for Molecular Medicine, Berlin, Germany, 2Dept. of Paediatric Pneumology and Immunology, Humboldt-University, Berlin, Germany, 3Dept. of Paediatrics, University ”La Sapienza”, Rome, Italy, 4Dept. of Paediatrics, Örebro Medical Center Hospital, Örebro, Sweden, 5Dept. of Dermatology and Venereology, University Hospital, Rotterdam, The Netherlands, 6Dept. of Paediatrics, Marienhospital, Wesel, Germany, 7Kinderklinik Schwabing, Technical University, Munich, Germany, 8TOMESA-Fachklinik, Bad Salzschlirf, Germany, 9Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Germany

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC)
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax:  +49 (0) 30 94 06 - 38 33