Variants in a novel epidermal collagen gene (COL29A1) are associated with atopic dermatitis.
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.
Söderhäll
Cilla
C
Department of Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Germany.
Marenholz
Ingo
I
Kerscher
Tamara
T
Rüschendorf
Franz
F
Esparza-Gordillo
Jorge
J
Worm
Margitta
M
Gruber
Christoph
C
Mayr
Gabriele
G
Albrecht
Mario
M
Rohde
Klaus
K
Schulz
Herbert
H
Wahn
Ulrich
U
Hubner
Norbert
N
Lee
Young-Ae
YA
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
C524742:COL6A5 protein, human; D024142:Collagen Type VI; D003094:Collagen