title: Genetic variation in the epidermal transglutaminase genes is not associated with atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common chronic inflammatory skin disorder where epidermal barrier dysfunction is a major factor in the pathogenesis. The identification of AD susceptibility genes related to barrier dysfunction is therefore of importance. The epidermal transglutaminases (TGM1, TGM3 and TGM5) encodes essential cross-linking enzymes in the epidermis.
  
  
  OBJECTIVE
  To determine whether genetic variability in the epidermal transglutaminases contributes to AD susceptibility.
  
  
  METHODS
  Forty-seven single nucleotide polymorphisms (SNPs) in the TGM1, TGM3 and TGM5 gene region were tested for genetic association with AD, independently and in relation to FLG genotype, using a pedigree disequilibrium test (PDT) in a Swedish material consisting of 1753 individuals from 539 families. In addition, a German case-control material, consisting of 533 AD cases and 1996 controls, was used for in silico analysis of the epidermal TGM regions. Gene expression of the TGM1, TGM3 and TGM5 gene was investigated by relative quantification with Real Time PCR (qRT-PCR). Immunohistochemical (IHC) analysis was performed to detect TG1, TG3 and TG5 protein expression in the skin of patients and healthy controls.
  
  
  RESULTS
  PDT analysis identified a significant association between the TGM1 SNP rs941505 and AD with allergen-specific IgE in the Swedish AD family material. However, the association was not replicated in the German case-control material. No significant association was detected for analyzed SNPs in relation to FLG genotype. TG1, TG3 and TG5 protein expression was detected in AD skin and a significantly increased TGM3 mRNA expression was observed in lesional skin by qRT-PCR.
  
  
  CONCLUSIONS
  Although TGM1 and TGM3 may be differentially expressed in AD skin, the results from the genetic analysis suggest that genetic variation in the epidermal transglutaminases is not an important factor in AD susceptibility.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agne
authors.initials: A
authors.lastname: Liedén
authors.forename: Mårten C G
authors.initials: MC
authors.lastname: Winge
authors.forename: Annika
authors.initials: A
authors.lastname: Sääf
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ekelund
authors.forename: Elke
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Maria
authors.initials: M
authors.lastname: Tengvall-Linder
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Wahlgren
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.forename: Maria
authors.initials: M
authors.lastname: Bradley
mesh_terms: D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013548:Sweden; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D012333:RNA, Messenger; C418703:transglutaminase 5; C498712:TGM3 protein, human; D011503:Transglutaminases; C105804:transglutaminase 1