Open AccessVariants in a Novel Epidermal Collagen Gene (COL29A1) Are Associated with Atopic Dermatitis
Author(s) -
Cilla Söderhäll,
Ingo Marenholz,
Tamara Kerscher,
Franz Rüschendorf,
Jorge Esparza-Gordillo,
Margitta Worm,
Christoph Grüber,
Gabriele Mayr,
Mario Albrecht,
Klaus Rohde,
Herbert Schulz,
Ulrich Wahn,
Norbert Hübner,
Youngae Lee
Publication year - 2007
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.0050242
Subject(s) - biology , atopic dermatitis , single nucleotide polymorphism , haplotype , candidate gene , hay fever , immunology , genetics , locus (genetics) , genetic linkage , genome wide association study , gene , asthma , allele , genotype
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.