Molecular evaluation of vitamin D responsiveness of healthy young adults.
Vitamin D3has via its metabolites 25-hydroxyvitamin D3(25(OH)D3) and 1α,25-dihydroxyvitamin D3(1,25(OH)2D3) 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 D3dose (2000μg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D3intake raised the average serum levels of both 25(OH)D3and 1,25(OH)2D3by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D3and 1,25(OH)2D3concentrations 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)D3concentrations. 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)D3serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334).
School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Sabine
S
Seuter
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Jyrki K
JK
Virtanen
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Tarja
T
Nurmi
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Jussi
J
Pihlajamäki
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Jaakko
J
Mursu
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Sari
S
Voutilainen
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Tomi-Pekka
TP
Tuomainen
School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Antonio
A
Neme
School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: carsten.carlberg@uef.fi.
Carsten
C
Carlberg
D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002762:Cholecalciferol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D014815:Vitamins / Q000494:pharmacology*; D055815:Young Adult; D020668:rap GTP-Binding Proteins / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D014815:Vitamins; C106907:WBP1 protein, human; D002762:Cholecalciferol; C065562:RAP2B protein, human; D020668:rap GTP-Binding Proteins; D002117:Calcitriol; D002112:Calcifediol
1,25(OH)(2)D(3); 25(OH)D(3); Accessible chromatin; FAIRE; In vivo human epigenome measurements; PBMCs; PTH; Vitamin D(3); Vitamin D(3) supplementation