A comprehensive analysis of the COL29A1 gene does not support a role in eczema

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• 作者：Aline Naumann MSc^a ; ^b ; ^* ; Cilla S&#xf6 ; derhä ; ll PhD^c ; ^* ; Regina F&#xf6 ; lster-Holst MD^d ; Hansj&#xf6 ; rg Baurecht MSc^a ; ^b ; ^e ; Viola Harde MD^d ; Konstanze Mü ; ller-Wehling MD^d ; Elke Rodrí ; guez PhD^b ; Andreas Ruether PhD^f ; Andre Franke PhD^f ; Stefan Wagenpfeil PhD^a ; ^e ; Natalija Novak MD^g ; Martin Mempel MD^b ; ^h ; Behnam Naderi Kalali PhDⁱ ; Michael Allgaeuer MScⁱ ; Jeanette Koch MScⁱ ; Markus Gerhard MDⁱ ; Erik Melé ; n MD^j ; ^k ; Carl-Fredrik Wahlgren PhD^l ; Inger Kull PhD^j ; ^m ; Caroline Stahl MSc^a ; G&#xf6 ; ran Pershagen MDⁿ ; Roger Lauener MD^o ; ^p ; Josef Riedler MD^q ; Gert Doekes PhD^r ; Annika Scheynius PhD^s ; Thomas Illig PhD^t ; Erika von Mutius MD^u ; Stefan Schreiber MD^f ; Juha Kere MD^c ; ^v ; Michael Kabesch MD^w ; ^* ; Stephan Weidinger MD^b ; ^d ; ^x ; ^* ; ^{weidinger@lrz.tum.de"" rel=""nofollow}
• 关键词：Atopic dermatitis ; eczema ; genetics ; Col29A1
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：127
• 期：5
• 页码：1187-1194.e7
• 全文大小：687 K

文摘

Background

Based on a recent positional cloning approach, it was claimed that the collagen 29A1 gene (COL29A1), which encodes an epidermal collagen, represents a major risk gene for eczema underlying a previously reported linkage to chromosome 3q21. However, thus far, not a single replication attempt has been published, and no definitive functional data have been provided.

Objectives

We aimed to determine whether COL29A1 polymorphisms contribute to eczema susceptibility and whether COL29A1 expression is altered in eczema.

Methods

We investigated the reported association of COL29A1 variants with eczema, subtypes of eczema, and eczema-related traits in 5 independent and large study populations comprehensively phenotyped for allergic diseases: a set of 1687 German patients with eczema and 2387 population control subjects, a collection of 274 German families with eczema-diseases children, a cross-sectional population of German children (n = 3099), the Swedish population-based birth cohort Children Allergy and Milieu in Stockholm, an Epidemiologic Study (BAMSE) (n = 2033), and the European cross-sectional Prevention of Allergy—Risk Factors for Sensitization Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 3113). An additional set of 19 COL29A1 coding single nucleotide polymorphisms was analyzed in BAMSE and PARSIFAL. COL29A1 expression was investigated by using in situ hybridization.

Results

We found no evidence for a relationship between COL29A1 polymorphisms and eczema. The equivalence test rejected the hypothesis of association even excluding small effects. In situ hybridization carried out on biopsy specimens from lesional and nonlesional skin of patients with eczema and from healthy control subjects did not show any differences in the cellular distribution pattern of COL29A1 expression at the mRNA level.

Conclusions

Our results suggest that COL29A1 is unlikely to contain genetic variants that have a major effect on eczema or atopy susceptibility.