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Association screening in the epidermal differentiation complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema

Item Type:Article
Title:Association screening in the epidermal differentiation complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema
Creators Name:Marenholz, I. and Rivera, V.A. and Esparza-Gordillo, J. and Bauerfeind, A. and Lee-Kirsch, M.A. and Ciechanowicz, A. and Kurek, M. and Piskackova, T. and Macek, M. and Lee, Y.A.
Abstract:The genetically determined impairment of the skin barrier is a primary cause of eczema. As numerous genes essential for an intact epidermis reside within the epidermal differentiation complex (EDC), we screened the National Center for Biotechnology Information (NCBI) database for putatively functional polymorphisms in the EDC genes and tested them for association with eczema. We identified 20 polymorphisms with predicted major impact on protein function. Of these, 4 were validated in 94 eczema patients: a nonsense mutation in FLG2 (rs12568784), a stop codon mutation in LCE1D (rs41268500), a 24-bp deletion in SPRR3 (rs28989168), and a frameshift mutation in S100A3 (rs11390146). The minor allele frequencies were 15.1, 6.1, 47.2, and 0.4%, respectively. Association testing of the validated polymorphisms in 555 eczema patients and 375 controls identified a significant effect of rs28989168 (SPRR3) on eczema. The association was replicated in another 1,314 cases and 1,322 controls, yielding an overall odds ratio of 1.30 (95% confidence interval 1.12-1.51; P=0.00067) for a dominant mode of inheritance. Small proline-rich proteins (SPRRs) are crossbridging proteins in the cornified cell envelope (CE), which provides the main barrier function of stratified squamous epithelia. The SPRR3 variant associated with eczema carried an extra 24-bp repeat in the central domain, which may alter the physical properties of the CE.
Source:Journal of Investigative Dermatology
ISSN:0022-202X
Publisher:Nature Publishing Group (U.S.A.)
Volume:131
Number:8
Page Range:1644-1649
Date:August 2011
Official Publication:https://doi.org/10.1038/jid.2011.90
PubMed:View item in PubMed

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