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

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onse t mainly in early childhood(1). It is commonly the initial clinical manifes tation of allergic disease, often preceding the onset of respiratory allerg ies(2,3). Along with asthma and allergic rhinitis, atopic dermatitis is an important manifestation of atopy that is characterized by the formation of allergy antibodies (IgE) to environmental allergens. In the developed count ries, the prevalence of atopic dermatitis is approximately 15%, with a stea dy increase over the past decades(4,5). Genetic and environmental factors i nteract to determine disease susceptibility and expression(6), and twin stu dies indicate that the genetic contribution is substantial(7). To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria(8, 9). A genome-wide linkage study revealed highly significant evidence for li nkage on chromosome 3q21 (Z(all)=4.31, P= 8.42x10(-6)). Moreover, this locu s provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71, alpha =44%), further sup porting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic derma titis and that the study of this disease opens new avenues to dissect the g enetics of atopy.