title: Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults.
abstract: 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).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinik für Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charité, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Heine
authors.forename: N
authors.initials: N
authors.lastname: Hoefer
authors.forename: A
authors.initials: A
authors.lastname: Franke
authors.forename: U
authors.initials: U
authors.lastname: Nöthling
authors.forename: R R
authors.initials: RR
authors.lastname: Schumann
authors.forename: L
authors.initials: L
authors.lastname: Hamann
authors.forename: M
authors.initials: M
authors.lastname: Worm
mesh_terms: D000328:Adult; D054458:Amplified Fragment Length Polymorphism Analysis; D016022:Case-Control Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human