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.

Three Novel Collagen VI Chains with High Homology to the α3 Chain

“…The protein sequence is, except for a single amino acid exchange, identical to the third potential splice variant presented here. As we have shown for mouse by RT-PCR, the collagen VI ␣5 chain is expressed in skin in man also (28). The expression in other tissues only partially overlaps; however intestine and lung also show expression in both species.…”

“…Interestingly, variants of the human COL6A5 gene were recently shown to be associated with atopic dermatitis (28). The authors of that study designated the human COL6A5 as COL29A1.…”

Three Novel Collagen VI Chains, α4(VI), α5(VI), and α6(VI)

“…DTT, dithiothreitol. N2 N3 N10 C2 N4 N5 N6 N7 N8 N9 N1 C2 C1 N1 C2 C1 N1 N2 N3 C2 C1 N4 N5 N6 N7 N1 N2 N3 C2 C1 N4 N5 N6 N7 C1 C C C C C N1 N2 N3 C2 C1 N4 N5 N6 N7 C3 ciation with atopic dermatitis (37). The COL29A1 gene appears to be the COL6A5 sequence reported here.…”

Colagenase de pescada branca: extração, purificação parcial, caracterização e teste de especificidade ao colágeno para aplicação industrial

“…It is the most abundant type, being widely distributed in the body as structures classically referred to as collagen fibrils that form bones, dentin, tendons, capsules bodies, corneal and dermal blood vessels. These structures are known to play an important role in the morphogenesis and cell metabolism of new tissue, providing mechanical and biochemical properties (MYLLYHARJU and KIVIRIKKO, 2004;SÖDERHÄLL et al, 2007;CHUNG and UITTO, 2010;DABOOR et al, 2010;FERREIRA et al, 2012;MAKAREEVA and LEIKIN, 2014). TURKIEWIC et al (1991) isolated a serine proteinase from Euphausia superba with collagenolytic properties, which was able to hydrolyze collagens from Achilles tendon type I and release fibrils of calfskin collagen, under conditions that do not denature the substrates.…”