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Liedén, A.* ; Winge, M.C.G.* ; Saaf, A.* ; Kockum, I.* ; Ekelund, E.* ; Rodriguez, E.* ; Fölster-Holst, R.* ; Franke, A.* ; Illig, T. ; Tengvall-Linder, M.* ; Baurecht, H.* ; Weidinger, S.* ; Wahlgren, C.-F.* ; Nordenskjöld, M.* ; Bradley, M.*

Genetic variation in the epidermal transglutaminase genes is not associated with atopic dermatitis.

PLoS ONE 7:e49694 (2012)
Verlagsversion Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
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. Conclusion: 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Of-function Variants ; Lamellar Ichthyosis ; Susceptibility Loci ; Linkage ; Eczema ; Skin ; Mutations ; Filaggrin ; Families ; Population
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 7, Heft: 11, Seiten: , Artikelnummer: e49694 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed