title: Variants in a novel epidermal collagen gene (COL29A1) are associated with atopic dermatitis.
abstract: 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.
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Ingo
authors.initials: I
authors.lastname: Marenholz
authors.forename: Tamara
authors.initials: T
authors.lastname: Kerscher
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Jorge
authors.initials: J
authors.lastname: Esparza-Gordillo
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.forename: Christoph
authors.initials: C
authors.lastname: Gruber
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mayr
authors.forename: Mario
authors.initials: M
authors.lastname: Albrecht
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohde
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003094:Collagen / Q000235:genetics*; D024142:Collagen Type VI; D003876:Dermatitis, Atopic / Q000209:etiology / Q000235:genetics*; D005192:Family Health; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D040582:Inheritance Patterns; D008969:Molecular Sequence Data; D014018:Tissue Distribution
chemical_list: C524742:COL6A5 protein, human; D024142:Collagen Type VI; D003094:Collagen