title: A comprehensive analysis of the COL29A1 gene does not support a role in eczema.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute for Medical Statistics and Epidemiology IMSE, Technische Universität München, Munich, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Naumann
authors.forename: Cilla
authors.initials: C
authors.lastname: Söderhäll
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Viola
authors.initials: V
authors.lastname: Harde
authors.forename: Konstanze
authors.initials: K
authors.lastname: Müller-Wehling
authors.forename: Elke
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
authors.forename: Behnam Naderi
authors.initials: BN
authors.lastname: Kalali
authors.forename: Michael
authors.initials: M
authors.lastname: Allgaeuer
authors.forename: Jeanette
authors.initials: J
authors.lastname: Koch
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: Inger
authors.initials: I
authors.lastname: Kull
authors.forename: Caroline
authors.initials: C
authors.lastname: Stahl
authors.forename: Göran
authors.initials: G
authors.lastname: Pershagen
authors.forename: Roger
authors.initials: R
authors.lastname: Lauener
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.forename: Gert
authors.initials: G
authors.lastname: Doekes
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004485:Eczema / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D017403:In Situ Hybridization; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000378:metabolism; D013548:Sweden
chemical_list: C524742:COL6A5 protein, human; D024142:Collagen Type VI