Klinik für Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charité, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Br J Dermatol. 2013 Apr;168(4):855-8. doi: 10.1111/bjd.12077. Epub 2013 Mar 13.
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).
To investigate the frequency of four common VDR gene polymorphisms in patients with AD, and their potential functional relevance.
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.
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.
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.
维生素 D 具有免疫调节功能，并且在过敏疾病中具有有益作用。已知维生素 D 受体基因（VDR）多态性，但尚未在特应性皮炎（AD）患者中进行研究。
研究 AD 患者中四种常见 VDR 基因多态性的频率及其潜在的功能相关性。
在这项病例对照研究中，通过限制性片段长度多态性分析，对 265 例 AD 患者（n=142 例重度 AD，SCORAD > 40；n=123 例中度 AD，SCORAD 15-40）和 265 例健康对照者进行了四种常见 VDR 基因多态性的基因分型。对 VDR 单倍型序列进行了计算机分析。通过定量逆转录-聚合酶链反应分析纯合 VDR 单倍型携带者单核细胞中 VDR 和维生素 D 代谢酶 CYP24A1 的基础表达和激活诱导表达。
与健康对照组相比，重度 AD 患者的 VDR BsmI（rs1544410）G 等位基因、ApaI（rs7975232）C 等位基因和 TaqI（rs731236）T 等位基因过度表达。这些单核苷酸多态性（SNP）紧密连锁，VDR 单倍型 GCT 与重度 AD 相关，互补 AAC 与 AD 保护相关。VDR 单倍型 GCT 区域在进化上是保守的。VDR FokI（rs2228570）SNP 与 AD 无关。单核细胞中 VDR 的基础表达和短期激活与单倍型无关。
严重 AD 患者中特定的 VDR 单倍型更为常见。这些数据表明 VDR 有助于 AD 的控制，例如通过调节表皮屏障功能和/或局部免疫反应。
