TY - JOUR
T1 - A comprehensive analysis of the COL29A1 gene does not support a role in eczema
AU - Naumann, Aline
AU - Söderhäll, Cilla
AU - Fölster-Holst, Regina
AU - Baurecht, Hansjörg
AU - Harde, Viola
AU - Müller-Wehling, Konstanze
AU - Rodríguez, Elke
AU - Ruether, Andreas
AU - Franke, Andre
AU - Wagenpfeil, Stefan
AU - Novak, Natalija
AU - Mempel, Martin
AU - Kalali, Behnam Naderi
AU - Allgaeuer, Michael
AU - Koch, Jeanette
AU - Gerhard, Markus
AU - Melén, Erik
AU - Wahlgren, Carl Fredrik
AU - Kull, Inger
AU - Stahl, Caroline
AU - Pershagen, Göran
AU - Lauener, Roger
AU - Riedler, Josef
AU - Doekes, Gert
AU - Scheynius, Annika
AU - Illig, Thomas
AU - Von Mutius, Erika
AU - Schreiber, Stefan
AU - Kere, Juha
AU - Kabesch, Michael
AU - Weidinger, Stephan
N1 - Funding Information:
Supported by grants of the German Research Council (DFG) (grant WE 2678/6-1 and Excellence Cluster “Inflammation at Interfaces”) and the German Ministry of Education and Research (BMBF) as part of the National Genome Research Network ( NGFN grants 01GS 0429 and 01GS 0818 ), the Christiane Kühne Center for Allergy Research and Education ( http://www.ck-care.ch/ ), the Graduate School of Information Science in Health of the Technische Universität München (TUM-GSISH), the COST SKINBAD action, the PopGen biobank, the Swedish Research Council, the Swedish Asthma and Allergy Association, Stockholm County Council, the Centre for Allergy Research, and Karolinska Institute. S.W. is supported by a Heisenberg fellowship of the DFG ( WE 2678/4-1 ). N.N. is supported by a Heisenberg-Professorship of the DFG ( NO454/-52 ). C.S. is the recipient of a scholarship from the Swedish Society of Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
Disclosure of potential conflict of interest: N. Novak receives research support from the German Research Council . C.-F. Wahlgren receives research support from the Swedish Asthma and Allergy Association . R. Lauener receives research support from the Kuhne Foundation and the European Union . E. von Mutius has consultant arrangements with GlaxoSmithKline, ProtectImmun, and Novartis and receives research support from Airsonett AB. S. Schreiber receives research support from the DFG, the BMBF, and the European Union . M. Kabesch has financial interests in Roxall, Glaxo Wellcome, Novartis, Sanofi Aventis, Allergopharma, and MSD and receives research support from the DFG, the BMBF, and the European Union . S. Weidinger receives research support from the DFG, the BMBF, and the European Union . The rest of the authors have declared that they have no conflict of interest.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Atopic dermatitis
KW - Col29A1
KW - eczema
KW - genetics
UR - http://www.scopus.com/inward/record.url?scp=79955582336&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2010.12.1123
DO - 10.1016/j.jaci.2010.12.1123
M3 - Article
AN - SCOPUS:79955582336
SN - 0091-6749
VL - 127
SP - 1187-1194.e7
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -