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

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.

High resolution 1H NMR of a lipid cubic phase using a solution NMR probe.

The cubic mesophase formed by monoacylglycerols and water is an important medium for the in meso crystallogenesis of membrane proteins. To investigate molecular level lipid and additive interactions within the cubic phase, a method was developed for improving the resolution of (1)H NMR spectra when using a conventional solution state NMR probe. Using this approach we obtained well-resolved J-coupling multiplets in the one-dimensional NMR spectrum of the cubic-Ia3d phase prepared with hydrated monoolein. A high resolution t-ROESY two-dimensional (1)H NMR spectrum of the cubic-Ia3d phase is also reported. Using this new methodology, we have investigated the interaction of two additive molecules, L-tryptophan and ruthenium-tris(2,2-bipyridyl) dichloride (rubipy), with the cubic mesophase. Based on the measured chemical shift differences when changing from an aqueous solution to the cubic phase, we conclude that L-tryptophan experiences specific interactions with the bilayer interface, whereas rubipy remains in the aqueous channels and does not associate with the lipid bilayer.