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

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood(1). It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies(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 countries, the prevalence of atopic dermatitis is approximately 15%, with a steady increase over the past decades(4,5). Genetic and environmental factors interact to determine disease susceptibility and expression(6), and twin studies 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 linkage on chromosome 3q21 (Z(all)=4.31, P= 8.42x10(-6)). Moreover, this locus provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71, alpha =44%), further supporting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic dermatitis and that the study of this disease opens new avenues to dissect the genetics of atopy.