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

Abstract

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies. 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. Genetic and environmental factors interact to determine disease susceptibility and expression, and twin studies indicate that the genetic contribution is substantial. To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria. A genome-wide linkage study revealed highly significant evidence for linkage on chromosome 3q21 (Zall=4.31, P= 8.42 10(-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.

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal allergic rhinitis in Japanese families

“…Recently, a genome-wide linkage scan identified a novel susceptibility locus for atopic dermatitis, that has not been reported for asthma or atopy-related phenotypes. 9 The development of seasonal allergic rhinitis (SAR), which is also referred to as hereditary allergic diathesis, is primarily dependent upon the degree of IgE antibody response to a specific pollen. It is suggested that IgE antibody responses to pollen may be controlled by genes associated with a particular HLA haplotype.…”

Atopic eczema/dermatitis syndrome – a genetically complex disease. New advances in discovering the genetic contribution

“…In a very recent study, evidence for linkage of AD (AEDS) to chromosome 3q21 near marker D3S3606 was detected (43). It was only under the assumption of paternal imprinting that significant evidence for linkage of allergic sensitization was detected to this locus, indicating that this trait is predominantly transmitted by the mother (43).…”

“…It was only under the assumption of paternal imprinting that significant evidence for linkage of allergic sensitization was detected to this locus, indicating that this trait is predominantly transmitted by the mother (43).…”

Clinical correlations of recent developments in the pathogenesis of atopic dermatitis

“…Genome screens have identified at least 4 regions of genetic linkage to AD on chromosomes 1q, 3q, 3p and 17q. 32,[139][140][141] Other mapped loci using composite phenotypes of AD and asthma combined have shown genetic linkage to chromosome 20p.32 Composite phenotypes for AD with increased total serum IgE (16q) 32 and allergen specific IgE (3p, 4p, 18q)140 have also been reported. Overlap of some of these loci with psoriasis (1q, 3q, 17q, 20p) 32 138 A brief description for some of the genes is outlined below.…”