Seuter Sabine, Virtanen Jyrki K, Nurmi Tarja, Pihlajamäki Jussi, Mursu Jaakko, Voutilainen Sari, Tuomainen Tomi-Pekka, Neme Antonio, Carlberg Carsten
School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
J Steroid Biochem Mol Biol. 2017 Nov;174:314-321. doi: 10.1016/j.jsbmb.2016.06.003. Epub 2016 Jun 6.
Vitamin D has via its metabolites 25-hydroxyvitamin D (25(OH)D) and 1α,25-dihydroxyvitamin D (1,25(OH)D) direct effects on the transcriptome and the epigenome of most human cells. In the VitDbol study we exposed 35 healthy young adults to an oral vitamin D dose (2000μg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D intake raised the average serum levels of both 25(OH)D and 1,25(OH)D by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D and 1,25(OH)D concentrations ranging from 277 to 1365. Interestingly, average serum parathyroid hormone (PTH) levels increased at day 1 by some 10% but then decreased within the following four weeks to levels 5% below baseline. In peripheral blood mononuclear cells (PBMCs) that were isolated at the same time points we determined vitamin D-modulated chromatin accessibility by FAIRE-qPCR at selected genomic loci. This method is well suited to evaluate both short-term and long-term in vivo effects of vitamin D on the epigenome of human subjects. The differential vitamin D responsiveness of the VitDbol study participants was determined via individual changes in their PTH levels or chromatin accessibility in relation to alterations in 25(OH)D concentrations. This led to the segregation of the subjects into 14 high, 11 mid and 10 low responders. In summary, the vitamin D responsiveness classification provides additional information compared to a vitamin D status assessment based on single 25(OH)D serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334).
维生素D通过其代谢产物25-羟基维生素D（25(OH)D）和1α,25-二羟基维生素D（1,25(OH)D）对大多数人类细胞的转录组和表观基因组产生直接影响。在VitDbol研究中，我们让35名健康的年轻成年人服用口服维生素D剂量（2000μg）或安慰剂，并在补充前以及第1、2和30天采集血样。在24小时内，维生素D摄入量使25(OH)D和1,25(OH)D的平均血清水平提高了约20%。然而，我们观察到这些血清水平存在很大的个体差异，25(OH)D和1,25(OH)D浓度之间的平均比值在277至1365之间。有趣的是，平均血清甲状旁腺激素（PTH）水平在第1天增加了约10%，但在接下来的四周内下降至低于基线水平5%。在同一时间点分离的外周血单核细胞（PBMCs）中，我们通过FAIRE-qPCR在选定的基因组位点测定了维生素D调节的染色质可及性。该方法非常适合评估维生素D对人类受试者表观基因组的短期和长期体内影响。通过VitDbol研究参与者的PTH水平或染色质可及性相对于25(OH)D浓度变化的个体变化，确定了他们对维生素D的不同反应性。这导致受试者被分为14名高反应者、11名中反应者和10名低反应者。总之，与基于单次25(OH)D血清测量的维生素D状态评估相比，维生素D反应性分类提供了额外的信息。该研究已在Clinicaltrials.gov（NCT02063334）注册。
