Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults

Summary Background  Vitamin D mediates immunomodulatory functions, and beneficial functions in allergic diseases have been suggested. Vitamin D receptor gene (VDR) polymorphisms are known but have not been studied in patients with atopic dermatitis (AD). Objectives  To investigate the frequency of f...

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Published inBritish journal of dermatology (1951) Vol. 168; no. 4; pp. 855 - 858
Main Authors Heine, G., Hoefer, N., Franke, A., Nöthling, U., Schumann, R.R., Hamann, L., Worm, M.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.04.2013
Wiley-Blackwell
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Summary:Summary Background  Vitamin D mediates immunomodulatory functions, and beneficial functions in allergic diseases have been suggested. Vitamin D receptor gene (VDR) polymorphisms are known but have not been studied in patients with atopic dermatitis (AD). Objectives  To investigate the frequency of four common VDR gene polymorphisms in patients with AD, and their potential functional relevance. Methods  In this case–control study, 265 patients with AD [n = 142 severe AD, Scoring AD index (SCORAD) > 40; n = 123 moderate AD, SCORAD 15–40] and 265 healthy controls were genotyped for four common VDR gene polymorphisms by restriction fragment length polymorphism analysis. The VDR haplotype sequences were analysed in silico. Baseline and activation‐induced gene expression of VDR and the vitamin D metabolizing enzyme CYP24A1 were analysed in monocytes of homozygous VDR haplotype carriers by quantitative reverse transcription–polymerase chain reaction. Results  In patients with severe AD, the VDR BsmI (rs1544410) G allele, ApaI (rs7975232) C allele and TaqI (rs731236) T alleles were over‐represented compared with healthy controls. These single nucleotide polymorphisms (SNP) were tightly linked, and the VDR haplotype GCT was correlated with severe AD and complementary AAC with protection from AD. The VDR haplotype GCT region is evolutionarily conserved. The VDR FokI (rs2228570) SNP was not associated with AD. Baseline VDR expression in monocytes and short‐term activation were haplotype independent. Conclusion  A specific VDR haplotype is more frequent in patients with severe AD. These data indicate that VDR contributes to the control of AD, e.g. by regulation of the epidermal barrier function and/or local immune response. What’s already known about this topic? • A role of vitamin D in the pathogenesis of atopic dermatitis (AD) is suggested by epidemiological and experimental data. • Genetic variants in the vitamin D receptor gene (VDR) are known, but their presence has not been investigated in patients with AD. What does this study add? • We show that, in patients with severe AD, specific single nucleotide polymorphisms in the VDR gene are significantly over‐represented. This implies the need to consider the VDR genotype of probands in vitamin D‐related clinical studies examining vitamin D in AD, and the need for further mechanistic research.
Bibliography:istex:E648FFA469419C0EA145B162488AC8FA2353986E
ArticleID:BJD12077
ark:/67375/WNG-TPWTSZ94-H
Funding sources 
This work was supported by grants to M.W. from the Deutsche Forschungsgemeinschaft (DFG–SFB650), the Investitionsbank Bank Berlin (IBB‐Katapult 1) and by the Charité– Universitätsmedizin Berlin. G.H. was supported by the Deutsche Forschungsgemeinschaft.
Conflicts of interest 
None declared.G.H. and N.H. contributed equally to this work; L.H. and M.W. share senior authorship of this work.
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ISSN:0007-0963
1365-2133
DOI:10.1111/bjd.12077