Atopic dermatitis (AD) is a common chronic inflammatory skin disorder and a major manifestation of allergic disease. AD typically presents in early childhood often preceding the onset of an allergic airway disease, such as asthma or hay fever. We previously mapped a susceptibility locus for AD on Chromosome 3q21. To identify the underlying disease gene, we used a dense map of microsatellite markers and single nucleotide polymorphisms, and we detected association with AD. In concordance with the linkage results, we found a maternal transmission pattern. Furthermore, we demonstrated that the same families contribute to linkage and association. We replicated the association and the maternal effect in a large independent family cohort. A common haplotype showed strong association with AD (p = 0.000059). The associated region contained a single gene, COL29A1, which encodes a novel epidermal collagen. COL29A1 shows a specific gene expression pattern with the highest transcript levels in skin, lung, and the gastrointestinal tract, which are the major sites of allergic disease manifestation. Lack of COL29A1 expression in the outer epidermis of AD patients points to a role of collagen XXIX in epidermal integrity and function, the breakdown of which is a clinical hallmark of AD.
Atopic dermatitis (AD, eczema) is a common chronic inflammatory skin disorder and a major manifestation of allergic disease. Typically, AD first occurs in early childhood, often preceding the onset of allergic airways disease, such as asthma and hay fever. A family history of allergic disorders is the single strongest predictor for AD, showing that genetic factors play a major role in the disease development. We have previously mapped a disease locus for AD on Chromosome 3q21, Now we have used a dense map of microsatellite markers and single nucleotide polymorphisms (SNPs) to find the underlying disease gene. We identified genetic markers in a subregion that showed association with AD, and replicated this finding in a large independent family cohort. The associated region contained a single gene, COL29A1, which encodes a novel collagen. We demonstrate that AD patients lack COL29A1 expression in the outer epidermis, implicating collagen XXIX in epidermal integrity and function. The gene expression pattern of COL29A1 in other organs, including the lung and the gut, suggests that this gene could have a role in a wider spectrum of allergic diseases and may provide a molecular link between AD and respiratory airways disease and food allergies.
The gene underlying atopic dermatitis susceptibility has been identified by gene mapping as expressing a novel collagen, whose expression is lacking in the outer epidermis of atopic dermatitis patients.