Loading...
 
Toggle Health Problems and D

Vitamin D - A master example of nutrigenomics – April 2023

Vitamin D - A master example of nutrigenomics

Redox Biology https://doi.org/10.1016/j.redox.2023.102695
Carsten Carlberg a b, Marianna Raczyk a, Natalia Zawrotna a

Image
Nutrigenomics attempts to characterize and integrate the relation between dietary molecules and gene expression on a genome-wide level. One of the biologically active nutritional compounds is vitamin D3, which activates via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) the nuclear receptor VDR (vitamin D receptor). Vitamin D3 can be synthesized endogenously in our skin, but since we spend long times indoors and often live at higher latitudes where for many winter months UV-B radiation is too low, it became a true vitamin.
The ligand-inducible transcription factor VDR is expressed in the majority of human tissues and cell types, where it modulates the epigenome at thousands of genomic sites. In a tissue-specific fashion this results in the up- and downregulation of primary vitamin D target genes, some of which are involved in attenuating oxidative stress.
Vitamin D affects a wide range of physiological functions including the control of metabolism, bone formation and immunity. In this review, we will discuss how the epigenome- and transcriptome-wide effects of 1,25(OH)2D3 and its receptor VDR serve as a master example in nutrigenomics. In this context, we will outline the basis of a mechanistic understanding for personalized nutrition with vitamin D3.
 Download the PDF from VitaminDWiki

References (34 = Carlberg)
  1. Carlberg, C., Ulven, S. M. & Molnar, F. Nutrigenomics: how science works. Springer textbook, doi:10.1007/978-3-030-36948-4 (2020).
  2. Meyer, C. A. & Liu, X. S. Identifying and mitigating bias in next-generation sequencing methods for chromatin biology. Nat Rev Genet 15, 709-721, doi:10.1038/nrg3788 (2014).
  3. Ferguson, J. F. et al. Nutrigenomics, the microbiome, and gene-environment interactions: new directions in cardiovascular disease research, prevention, and treatment: a scientific statement from the American Heart Association. Circ Cardiovasc Genet 9, 291-313, doi:10.1161/HCG.0000000000000030 (2016).
  4. Fenech, M. et al. Nutrigenetics and Nutrigenomics: viewpoints on the current status and applications in nutrition research and practice. Journal of nutrigenetics and nutrigenomics 4, 69-89, doi:10.1159/000327772 (2011).
  5. Müller, M. & Kersten, S. Nutrigenomics: goals and strategies. Nat Rev Genet 4, 315322, doi:10.1038/nrg1047 (2003).
  6. Vanden Berghe, W. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes. Pharmacological research : the official journal of the Italian Pharmacological Society 65, 565-576, doi:10.1016/j.phrs.2012.03.007 (2012).
  7. Bendik, I., Friedel, A., Roos, F. F., Weber, P. & Eggersdorfer, M. Vitamin D: a critical and essential micronutrient for human health. Front Physiol 5, 248, doi:10.3389/fphys.2014.00248 (2014).
  8. Carlberg, C. Molecular endocrinology of vitamin D on the epigenome level. Mol Cell Endocrinol 453, 14-21, doi:10.1016/j.mce.2017.03.016 (2017).
  9. Hanel, A. & Carlberg, C. Time-resolved gene expression analysis monitors the regulation of inflammatory mediators and attenuation of adaptive immune response by vitamin D. Int J Mol Sci 23, doi:10.3390/ijms23020911 (2022).
  10. Malmberg, H. R., Hanel, A., Taipale, M., Heikkinen, S. & Carlberg, C. Vitamin D treatment sequence is critical for transcriptome modulation of immune challenged primary human cells. Frontiers in immunology 12, 754056, doi:10.3389/fimmu.2021.754056 (2021).
  11. Sosa-Diaz, E., Hernandez-Cruz, E. Y. & Pedraza-Chaverri, J. The role of vitamin D on redox regulation and cellular senescence. Free Radic Biol Med 193, 253-273, doi:10.1016/j.freeradbiomed.2022.10.003 (2022).
  12. Tremezaygues, L. et al. Cutaneous photosynthesis of vitamin D: an evolutionary highly-conserved endocrine system that protects against environmental hazards including UV-radiation and microbial infections. Anticancer Res 26, 2743-2748 (2006).
  13. Holick, M. F. Photobiology of vitamin D. Vitamin D 3rd edn, 13-22, doi:10.1016/b978-0-12-381978-9.10002-2 (2011).
  14. Capell-Hattam, I. M. & Brown, A. J. Sterol evolution: cholesterol synthesis in animals is less a required trait than an acquired taste. Curr Biol 30, R886-R888, doi:10.1016/j.cub.2020.06.007 (2020).
  15. Jasinghe, V. J., Perera, C. O. & Barlow, P. J. Bioavailability of vitamin D2 from irradiated mushrooms: an in vivo study. Br JNutr 93, 951-955 (2005).
  16. Holick, M. F. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80, 1678S-1688S (2004).
  17. Bouillon, R. & Suda, T. Vitamin D: calcium and bone homeostasis during evolution. BoneKEy Reports 3, 480, doi:10.1038/bonekey.2013.214 (2014).
  18. Tripkovic, L. et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am JClin Nutr 95, 1357-1364, doi:10.3945/ajcn.111.031070 (2012).
  19. Lamberg-Allardt, C. Vitamin D in foods and as supplements. Progress in biophysics and molecular biology 92, 33-38, doi:10.1016/j.pbiomolbio.2006.02.017 (2006).
  20. Bikle, D. D. & Schwartz, J. Vitamin D binding protein, total and free vitamin D levels in different physiological and pathophysiological conditions. Front Endocrinol 10, 317, doi:10.3389/fendo.2019.00317 (2019).
  21. Bikle, D. D. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21, 319-329, doi:10.1016/j.chembiol.2013.12.016 (2014).
  22. Norman, A. W. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88, 491S-499S (2008).
  23. Bikle, D. & Christakos, S. New aspects of vitamin D metabolism and action - addressing the skin as source and target. Nat Rev Endocrinol, doi:10.1038/s41574-019- 0312-5 (2020).
  24. Haussler, M. R., Jurutka, P. W., Mizwicki, M. & Norman, A. W. Vitamin D receptor (VDR)-mediated actions of 1a,25(OH)2vitamin D3: genomic and non-genomic mechanisms. Best practice & research. Clinical endocrinology & metabolism 25, 543559, doi:10.1016/j.beem.2011.05.010 (2011).
  25. Hewison, M. et al. Extra-renal 25-hydroxyvitamin D3-1a-hydroxylase in human health and disease. J Steroid Biochem Mol Biol 103, 316-321, doi:10.1016/j.jsbmb.2006.12.078 (2007).
  26. Zerwekh, J. E. Blood biomarkers of vitamin D status. Am J Clin Nutr 87, 1087S-1091S, doi:10.1093/ajcn/87.4.1087S (2008).
  27. Hollis, B. W. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 135, 317-322 (2005).
  28. Institute-of-Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press (2011).
  29. Bouillon, R. et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 29, 726-776 (2008).
  30. Sintzel, M. B., Rametta, M. & Reder, A. T. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther 7, 59-85, doi:10.1007/s40120-017-0086-4 (2018).
  31. Ramagopalan, S. V. et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS genetics 5, e1000369, doi:10.1371/journal.pgen.1000369 (2009).
  32. Jeffery, L. E., Raza, K. & Hewison, M. Vitamin D in rheumatoid arthritis-towards clinical application. Nat Rev Rheumatol 12, 201-210, doi:10.1038/nrrheum.2015.140 (2016).
  33. Fletcher, J., Cooper, S. C., Ghosh, S. & Hewison, M. The role of vitamin D in Inflammatory bowel disease: mechanism to management. Nutrients 11, doi:10.3390/nu11051019 (2019).
  34. Infante, M. et al. Influence of vitamin D on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients 11, doi:10.3390/nu11092185 (2019).
  35. Huang, S. J. et al. Vitamin D deficiency and the risk of tuberculosis: a meta-analysis. DrugDesDevel Ther 11, 91-102, doi:10.2147/DDDT.S79870 (2017).
  36. Rook, G. A. The role of vitamin D in tuberculosis. Am Rev Respir Dis 138, 768-770, doi:10.1164/ajrccm/138.4.768 (1988).
  37. Charoenngam, N., Shirvani, A. & Holick, M. F. Vitamin D and Its potential benefit for the COVID-19 pandemic. Endocrine practice : officialjournal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 27, 484493, doi:10.1016/j.eprac.2021.03.006 (2021).
  38. Maghbooli, Z. et al. Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS ONE 15, e0239799, doi:10.1371/journal.pone.0239799 (2020).
  39. Pludowski, P. et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev 12, 976-989, doi:10.1016/j.autrev.2013.02.004 (2013).
  40. Carlberg, C. Molecular approaches for optimizing vitamin D supplementation. Vitamins and hormones 100, 255-271, doi:10.1016/bs.vh.2015.10.001 (2016).
  41. Lu, Z. et al. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol 103, 642-644, doi:10.1016/j.jsbmb.2006.12.010 (2007).
  42. Urbain, P., Singler, F., Ihorst, G., Biesalski, H. K. & Bertz, H. Bioavailability of vitamin D2 from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25- hydroxyvitamin D: a randomized controlled trial. European journal of clinical nutrition 65, 965-971, doi:10.1038/ejcn.2011.53 (2011).
  43. Holick, M. F. et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin EndocrinolMetab 96, 1911-1930, doi:10.1210/jc.2011-0385 (2011).
  44. Cheskis, B. J., Freedman, L. P. & Nagpal, S. Vitamin D receptor ligands for osteoporosis. Curr Opin InvestigDrugs 7, 906-911 (2006).
  45. Krasowski, M. D., Ni, A., Hagey, L. R. & Ekins, S. Evolution of promiscuous nuclear hormone receptors: LXR, FXR, VDR, PXR, and CAR. Mol Cell Endocrinol 334, 3948, doi:10.1016/j.mce.2010.06.016 (2011).
  46. Makishima, M. et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313-1316, doi:10.1126/science.1070477 (2002).
  47. Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362-1365, doi:10.1126/science.284.5418.1362 (1999).
  48. Staudinger, J. L. et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 98, 3369-3374., doi:10.1073/pnas.051551698 (2001).
  49. Guo, G. L. et al. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem 278, 45062-45071, doi:10.1074/jbc.M307145200 (2003).
  50. Whitfield, G. K. et al. Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. Endocrinology 144, 2704-2716, doi:10.1210/en.2002-221101 (2003).
  51. Hanel, A. & Carlberg, C. Vitamin D and evolution: pharmacologic implications. Biochem Pharmacol 173, 113595, doi:10.1016/j.bcp.2019.07.024 (2020).
  52. Meyer, M. B. & Pike, J. W. Genomic mechanisms controlling renal vitamin D metabolism. J Steroid Biochem Mol Biol 228, 106252, doi:10.1016/j.jsbmb.2023.106252 (2023).
  53. Heikkinen, S. et al. Nuclear hormone 1a,25-dihydroxyvitamin D3 elicits a genomewide shift in the locations of VDR chromatin occupancy. Nucleic Acids Res 39, 91819193, doi:10.1093/nar/gkr654 (2011).
  54. Vanherwegen, A. S. et al. Vitamin D controls the capacity of human dendritic cells to induce functional regulatory T cells by regulation of glucose metabolism. J Steroid Biochem Mol Biol 187, 134-145, doi:10.1016/j.jsbmb.2018.11.011 (2019).
  55. Vanherwegen, A. S., Gysemans, C. & Mathieu, C. Vitamin D endocrinology on the cross-road between immunity and metabolism. Mol Cell Endocrinol 453, 52-67, doi:10.1016/j.mce.2017.04.018 (2017).
  56. Chun, R. F., Liu, P. T., Modlin, R. L., Adams, J. S. & Hewison, M. Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol 5, 151, doi:10.3389/fphys.2014.00151 (2014).
  57. Gombart, A. F. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 4, 1151-1165, doi:10.2217/fmb.09.87 (2009).
  58. Zanoni, I. & Granucci, F. Role of CD14 in host protection against infections and in metabolism regulation. Front Cell Infect Microbiol 3, 32, doi:10.3389/fcimb.2013.00032 (2013).
  59. Lu, M., McComish, B. J., Burdon, K. P., Taylor, B. V. & Korner, H. The association between vitamin D and multiple sclerosis risk: 1,25(OH)2D3 induces super-enhancers bound by VDR. Frontiers in immunology 10, 488, doi:10.3389/fimmu.2019.00488 (2019).
  60. Dankers, W., Colin, E. M., van Hamburg, J. P. & Lubberts, E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Frontiers in immunology 7, 697, doi:10.3389/fimmu.2016.00697 (2016).
  61. Carlberg, C. & Velleuer, E. Molecular immunology: how science works. Springer Textbook (2022).
  62. Zanoni, I., Tan, Y., Di Gioia, M., Springstead, J. R. & Kagan, J. C. By capturing inflammatory lipids released from dying cells, the receptor CD14 induces inflammasome-dependent phagocyte hyperactivation. Immunity 47, 697-709 e693, doi:10.1016/j.immuni.2017.09.010 (2017).
  63. Hoeksema, M. A. & de Winther, M. P. Epigenetic regulation of monocyte and macrophage function. AntioxidRedox Signal 25, 758-774, doi:10.1089/ars.2016.6695 (2016).
  64. Liang, S., Cai, J., Li, Y. & Yang, R. 1,25Dihydroxyvitamin D3 induces macrophage polarization to M2 by upregulating T cell Igmucin 3 expression. Mol Med Rep 19, 37073713, doi:10.3892/mmr.2019.10047 (2019).
  65. Novershtern, N. et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 144, 296-309, doi:10.1016/j.cell.2011.01.004 (2011).
  66. Cortes, M. et al. Developmental vitamin D availability impacts hematopoietic stem cell production. Cell reports 17, 458-468, doi:10.1016/j.celrep.2016.09.012 (2016).
  67. Koivisto, O., Hanel, A. & Carlberg, C. Key vitamin D target genes with functions in the immune system. Nutrients 12, doi:10.3390/nu12041140 (2020).
  68. Zeitelhofer, M. et al. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 114, E1678-E1687, doi:10.1073/pnas.1615783114 (2017).
  69. Barragan, M., Good, M. & Kolls, J. K. Regulation of dendritic cell function by vitamin D. Nutrients 7, 8127-8151, doi:10.3390/nu7095383 (2015).
  70. Sever, R. & Brugge, J. S. Signal transduction in cancer. Cold Spring Harb Perspect Med 5, doi:10.1101/cshperspect.a006098 (2015).
  71. Meyer, M. B., Goetsch, P. D. & Pike, J. W. VDR/RXR and TCF4/beta-catenin cistromes in colonic cells of colorectal tumor origin: impact on c-FOS and c-MYC gene expression. Mol Endocrinol 26, 37-51, doi:10.1210/me.2011-1109 (2012).
  72. Palmer, H. G. et al. Genetic signatures of differentiation induced by 1a,25- dihydroxyvitamin D3 in human colon cancer cells. Cancer Res 63, 7799-7806 (2003).
  73. Wood, R. J., Tchack, L., Angelo, G., Pratt, R. E. & Sonna, L. A. DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics 17, 122-129, doi:10.1152/physiolgenomics.00002.2003 (2004).
  74. Salehi-Tabar, R. et al. Vitamin D receptor as a master regulator of the c-MYC/MXD1 network. Proc Natl Acad Sci U S A 109, 18827-18832, doi:10.1073/pnas.1210037109 (2012).
  75. Sinkkonen, L., Malinen, M., Saavalainen, K., Vaisanen, S. & Carlberg, C. Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter. Nucleic Acids Res 33, 2440-2451, doi:10.1093/nar/gki502 (2005).
  76. Saramaki, A., Banwell, C. M., Campbell, M. J. & Carlberg, C. Regulation of the human p21waf1/cip1 gene promoter via multiple binding sites for p53 and the vitamin D3 receptor. Nucleic Acids Res 34, 543-554, doi:10.1093/nar/gkj460 (2006).
  77. Saramaki, A. et al. Cyclical chromatin looping and transcription factor association on the regulatory regions of the p21 (CDKN1A) gene in response to 1a,25- dihydroxyvitamin D3. J Biol Chem 284, 8073-8082, doi:10.1074/jbc.M808090200 (2009).
  78. Toropainen, S., Vaisanen, S., Heikkinen, S. & Carlberg, C. The down-regulation of the human MYC gene by the nuclear hormone 1a,25-dihydroxyvitamin D3 is associated with cycling of corepressors and histone deacetylases. J Mol Biol 400, 284-294, doi:10.1016/j.jmb.2010.05.031 (2010).
  79. Abe, E. et al. Differentiation of mouse myeloid leukemia cells induced by 1a,25- dihydroxyvitamin D3. Proc Natl Acad Sci USA 78, 4990-4994 (1981).
  80. Colston, K., Colston, M. J., Fieldsteel, A. H. & Feldman, D. 1,25-dihydroxyvitamin D3 receptors in human epithelial cancer cell lines. Cancer Research 42, 856-859 (1982).
  81. Balomenos, D. et al. The cell cycle inhibitor p21 controls T-cell proliferation and sex- linked lupus development. Nat Med 6, 171-176, doi:10.1038/72272 (2000).
  82. Martinez-Lostao, L., Anel, A. & Pardo, J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res 21, 5047-5056, doi:10.1158/1078-0432.CCR-15-0685 (2015).
  83. Doherty, A. H., Ghalambor, C. K. & Donahue, S. W. Evolutionary physiology of bone: bone metabolism in changing environments. Physiology (Bethesda) 30, 17-29, doi:10.1152/physiol.00022.2014 (2015).
  84. van de Peppel, J. & van Leeuwen, J. P. Vitamin D and gene networks in human osteoblasts. Front Physiol 5, 137, doi:10.3389/fphys.2014.00137 (2014).
  85. van Driel, M. & van Leeuwen, J. Vitamin D and Bone: A Story of Endocrine and Auto/Paracrine Action in Osteoblasts. Nutrients 15, doi:10.3390/nu15030480 (2023).
  86. Latic, N. & Erben, R. G. Interaction of vitamin D with peptide hormones with emphasis on parathyroid hormone, FGF23, and the renin-angiotensin-aldosterone system. Nutrients 14, doi:10.3390/nu14235186 (2022).
  87. Veldurthy, V. et al. Vitamin D, calcium homeostasis and aging. Bone Res 4, 16041, doi:10.1038/boneres.2016.41 (2016).
  88. Bar, L. et al. Insulin suppresses the production of fibroblast growth factor 23 (FGF23). Proc Natl Acad Sci U S A 115, 5804-5809, doi:10.1073/pnas.1800160115 (2018).
  89. Hanel, A. et al. Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood. Scientific reports 10, 21051, doi:10.1038/s41598-020-78288-0 (2020).
  90. McCarthy, K. et al. Association between vitamin D deficiency and the risk of prevalent type 2 diabetes and incident prediabetes: A prospective cohort study using data from The Irish Longitudinal Study on Ageing (TILDA). EClinicalMedicine 53, 101654, doi:10.1016/j.eclinm.2022.101654 (2022).
  91. Melguizo-Rodriguez, L. et al. Role of Vitamin D in the Metabolic Syndrome. Nutrients 13, doi:10.3390/nu13030830 (2021).
  92. Kim-Hellmuth, S. et al. Cell type-specific genetic regulation of gene expression across human tissues. Science 369, doi:10.1126/science.aaz8528 (2020).
  93. Carlberg, C. & Molnar, F. The impact of chromatin. Mechanisms of Gene Regulation, 2nded., Springer, 17-34, doi:DOI: 10.1007/978-94-017-7741-4_2 (2016).
  94. Michael, A. K. & Thoma, N. H. Reading the chromatinized genome. Cell 184, 35993611, doi:10.1016/j.cell.2021.05.029 (2021).
  95. Beisel, C. & Paro, R. Silencing chromatin: comparing modes and mechanisms. Nat Rev Genet 12, 123-135, doi:10.1038/nrg2932 (2011).
  96. Rivera, Chloe M. & Ren, B. Mapping human epigenomes. Cell 155, 39-55, doi:10.1016/j.cell.2013.09.011 (2013).
  97. Hathaway, N. A. et al. Dynamics and memory of heterochromatin in living cells. Cell 149, 1447-1460, doi:10.1016/j.cell.2012.03.052 (2012).
  98. Perino, M. & Veenstra, G. J. Chromatin control of developmental dynamics and plasticity. Dev Cell 38, 610-620, doi:10.1016/j.devcel.2016.08.004 (2016).
  99. Carlberg, C. & Molnar, F. The epigenome. Mechanisms of Gene Regulation, 2nd ed., Springer, 159-172, doi:DOI: 10.1007/978-94-017-7741-4_8 (2016).
  100. Li, J. et al. Metabolic control of histone acetylation for precise and timely regulation of minor ZGA in early mammalian embryos. CellDiscov 8, 96, doi:10.1038/s41421-022- 00440-z (2022).
  101. Su, C. et al. 3D chromatin maps of the human pancreas reveal lineage-specific regulatory architecture of T2D risk. Cell Metab 34, 1394-1409 e1394, doi:10.1016/j.cmet.2022.08.014 (2022).
  102. Bruno, S., Williams, R. J. & Del Vecchio, D. Epigenetic cell memory: the gene's inner chromatin modification circuit. PLoS computational biology 18, e1009961, doi:10.1371/journal.pcbi.1009961 (2022).
  103. Fitz-James, M. H. & Cavalli, G. Molecular mechanisms of transgenerational epigenetic inheritance. Nat Rev Genet 23, 325-341, doi:10.1038/s41576-021-00438-5 (2022).
  104. Carlberg, C. & Molnar, F. Chromatin modifiers. Mechanisms of Gene Regulation, 2nd ed., Springer, 129-145, doi:DOI: 10.1007/978-94-017-7741-4_8 (2016).
  105. Gut, P. & Verdin, E. The nexus of chromatin regulation and intermediary metabolism. Nature 502, 489-498, doi:10.1038/nature12752 (2013).
  106. Chen, C., Wang, Z. & Qin, Y. Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy. Frontiers in pharmacology 13, 935536, doi:10.3389/fphar.2022.935536 (2022).
  107. Dai, Z., Ramesh, V. & Locasale, J. W. The evolving metabolic landscape of chromatin biology and epigenetics. Nat Rev Genet 21, 737-753, doi:10.1038/s41576-020-0270-8 (2020).
  108. Carlberg, C., Ulven, S. M. & Molnar, F. Nutrigenomics. Springer Textbook (2016).
  109. Carlberg, C. & Molnar, F. Human epigenomics, Springer (2018).
  110. Pike, J. W. et al. Perspectives on mechanisms of gene regulation by 1,25- dihydroxyvitamin D3 and its receptor. J Steroid Biochem Mol Biol 103, 389-395 (2007).
  111. Mangelsdorf, D. J. & Evans, R. M. The RXR heterodimers and orphan receptors. Cell 83, 841-850 (1995).
  112. Carlberg, C. Genome-wide (over)view on the actions of vitamin D. Front Physiol 5, 167, doi:10.3389/fphys.2014.00167 (2014).
  113. Ramagopalan, S. V. et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome research 20, 1352-1360 (2010).
  114. Neme, A., Seuter, S. & Carlberg, C. Selective regulation of biological processes by vitamin D based on the spatio-temporal cistrome of its receptor. Biochim Biophys Acta 1860, 952-961, doi:10.1016/j.bbagrm.2017.07.002 (2017).
  115. Ding, N. et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell 153, 601-613, doi:10.1016/j.cell.2013.03.028 (2013).
  116. Tuoresmaki, P., Vaisanen, S., Neme, A., Heikkinen, S. & Carlberg, C. Patterns of
  117. genome-wide VDR locations. PLoS ONE 9, e96105, doi:10.1371/journal.pone.0096105 (2014).
  118. Molnár, F., Perakyla, M. & Carlberg, C. Vitamin D receptor agonists specifically modulate the volume of the ligand-binding pocket. J Biol Chem 281, 10516-10526, doi:10.1074/jbc.M513609200 (2006).
  119. Polly, P. et al. VDR-Alien: a novel, DNA-selective vitamin D3 receptor-corepressor partnership. Faseb J 14, 1455-1463 (2000).
  120. Herdick, M. & Carlberg, C. Agonist-triggered modulation of the activated and silent state of the vitamin D3 receptor by interaction with co-repressors and co-activators. J. Mol. Biol. 304, 793-801 (2000).
  121. Nurminen, V., Neme, A., Seuter, S. & Carlberg, C. The impact of the vitamin D- modulated epigenome on VDR target gene regulation. Biochim Biophys Acta 1861, 697-705, doi:10.1016/j.bbagrm.2018.05.006. (2018).
  122. Nurminen, V., Neme, A., Seuter, S. & Carlberg, C. Modulation of vitamin D signaling by the pioneer factor CEBPA. Biochim Biophys Acta 1862, 96-106, doi:10.1016/j.bbagrm.2018.12.004 (2019).
  123. Seuter, S., Neme, A. & Carlberg, C. Epigenome-wide effects of vitamin D and their impact on the transcriptome of human monocytes involve CTCF. Nucleic Acids Res 44, 4090-4104, doi:10.1093/nar/gkv1519 (2016).
  124. Zaret, K. S. & Carroll, J. S. Pioneer transcription factors: establishing competence for gene expression. Gen Dev 25, 2227-2241 (2011).
  125. Seuter, S., Neme, A. & Carlberg, C. Epigenomic PU.1-VDR crosstalk modulates vitamin D signaling. Biochim Biophys Acta 1860, 405-415, doi:10.1016/j.bbagrm.2017.02.005 (2017).
  126. Seuter, S., Neme, A. & Carlberg, C. ETS transcription factor family member GABPA contributes to vitamin D receptor target gene regulation. J Steroid Biochem Mol Biol 177, 46-52, doi:10.1016/j.jsbmb.2017.08.006 (2018).
  127. Carlberg, C. Vitamin D and is target genes. Nutrients 14, doi:10.3390/nu14071354 (2022).
  128. Saccone, D., Asani, F. & Bornman, L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene 561, 171-180,
  129. doi:10.1016/j.gene.2015.02.024 (2015).
  130. Pilon, C. et al. Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors. Int J Endocrinol 2015, 375349, doi:10.1155/2015/375349 (2015).
  131. Chandel, N., Malhotra, A. & Singhal, P. C. Vitamin D receptor and epigenetics in HIV infection and drug abuse. Front Microbiol 6, 788, doi:10.3389/fmicb.2015.00788 (2015).
  132. Jiang, C. et al. The methylation state of VDR gene in pulmonary tuberculosis patients. J Thorac Dis 9, 4353-4357, doi:10.21037/jtd.2017.09.107 (2017).
  133. Hussain, M. Z. et al. Genetic and expression deregulation of immunoregulatory genes in rheumatoid arthritis. Mol Biol Rep 48, 5171-5180, doi:10.1007/s11033-021-06518- 3 (2021).
  134. Sun, J., Zhang, S., Liu, J. S., Gui, M. & Zhang, H. Expression of vitamin D receptor in renal tissue of lupus nephritis and its association with renal injury activity. Lupus 28, 290-294, doi:10.1177/0961203319826704 (2019).
  135. Matos, C. et al. Downregulation of the vitamin D receptor expression during acute gastrointestinal graft versus host disease is associated with poor outcome after allogeneic stem cell transplantation. Frontiers in immunology 13, 1028850, doi:10.3389/fimmu.2022.1028850 (2022).
  136. Neme, A., Seuter, S. & Carlberg, C. Vitamin D-dependent chromatin association of
  137. CTCF in human monocytes. Biochim Biophys Acta 1859, 1380-1388, doi:10.1016/j.bbagrm.2016.08.008 (2016).
  138. Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380, doi:10.1038/nature11082 (2012).
  139. Genomes Project, C. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65, doi:10.1038/nature11632 (2012).
  140. Rieder, M. J. et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 352, 2285-2293, doi:10.1056/NEJMoa044503 (2005).
  141. Carlberg, C. & Haq, A. The concept of the personal vitamin D response index. J Steroid Biochem Mol Biol 175, 12-17, doi:10.1016/j.jsbmb.2016.12.011 (2018).
  142. Carlberg, C. et al. Primary vitamin D target genes allow a categorization of possible benefits of vitamin D3 ^supplementation. PLoS ONE 8, e71042, doi:10.1371/journal.pone.0071042 (2013).
  143. Wilfinger, J. et al. Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system. J. Nutr. Biochem. 25, 875-884 (2014).
  144. Ryynanen, J. et al. Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals. Mol Nutr Food Res 58, 20362045, doi:10.1002/mnfr.201400291 (2014).
  145. Saksa, N. et al. Dissecting high from low responders in a vitamin D3 intervention study. J Steroid Biochem Mol Biol 148, 275-282, doi:10.1016/jjsbmb.2014.11.012 (2015).
  146. Vukic, M. et al. Relevance of vitamin D receptor target genes for monitoring the vitamin D responsiveness of primary human cells. PLoS ONE 10, e0124339, doi:10.1371/journal.pone.0124339 (2015).
  147. Seuter, S. et al. Molecular evaluation of vitamin D responsiveness of healthy young adults. J Steroid Biochem Mol Biol 174, 314-321 (2017).
  148. Mangin, M., Sinha, R. & Fincher, K. Inflammation and vitamin D: the infection connection. Inflamm Res 63, 803-819, doi:10.1007/s00011-014-0755-z (2014).
  149. Salzer, J. et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 79, 2140-2145, doi:10.1212/WNL.0b013e3182752ea8 (2012).
  150. Fleet, J. C., DeSmet, M., Johnson, R. & Li, Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 441, 61-76, doi:10.1042/BJ20110744 (2012).
  151. Jiang, X. et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature communications 9, 260, doi:10.1038/s41467-017-02662-2 (2018).
  152. Prabhu, A. V., Luu, W., Li, D., Sharpe, L. J. & Brown, A. J. DHCR7: a vital enzyme switch between cholesterol and vitamin D production. Prog Lipid Res 64, 138-151, doi:10.1016/j.plipres.2016.09.003 (2016).
  153. Hanel, A., Veldhuizen, C. & Carlberg, C. Gene-regulatory potential of 25-hydroxyvitamin D3 and D2. Front Nutr 9, 910601, doi:10.3389/fnut.2022.910601 (2022).
  154. Seuter, S., Pehkonen, P., Heikkinen, S. & Carlberg, C. Dynamics of 1a,25-dihydroxyvitamin D-dependent chromatin accessibility of early vitamin D receptor target genes. Biochim Biophys Acta 1829, 1266-1275, doi:10.1016/j.bbagrm.2013.10.003 (2013).
  155. Kreienkamp, R. et al. Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes. Oncotarget, 30018-30031, doi:10.18632/oncotarget. 9065 (2016).
  156. Manson, J. E. et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380, 33-44, doi:10.1056/NEJMoa1809944 (2019).
  157. Chen, Y., Michalak, M. & Agellon, L. B. Importance of nutrients and nutrient metabolism on human health. Yale J Biol Med 91, 95-103 (2018).
  158. Ordovas, J. M., Ferguson, L. R., Tai, E. S. & Mathers, J. C. Personalised nutrition and health. Bmj 361, bmj k2173, doi:10.1136/bmj.k2173 (2018).
  159. Carlberg, C. et al. In vivo response of the human epigenome to vitamin D: a proof-of– principle study. J Steroid Biochem Mol Biol 180, 142-148, doi:10.1016/j.jsbmb.2018.01.002 (2018).
  160. Neme, A. et al. In vivo transcriptome changes of human white blood cells in response to vitamin D. J Steroid Biochem Mol Biol 188, 71-76, doi:10.1016/jjsbmb.2018.11.019 (2019).
  161. Verstuyf, A., Carmeliet, G., Bouillon, R. & Mathieu, C. Vitamin D: a pleiotropic hormone. Kidney international 78, 140-145 (2010).
  162. Carlberg, C. The physiology of vitamin D-far more than calcium and bone. Front Physiol 5, 335, doi:10.3389/fphys.2014.00335 (2014).
See also by Carlberg in VitaminDWiki

6 of 6,980 results for nutrigenomics "vitamin d" in Google Scholar (Oct 2024)

  • Nongenomic Activities of Vitamin D - Dec 2022 FREE PDF
  • Using nutrigenomics to guide personalized nutrition supplementation for bolstering immune system - Jan 2023 c10.1007/s13755-022-00208-5|FREE PDF]
  • Nutrigenomics in Autoimmune Disease - 2024 Nutrigenomics in Autoimmune Disease - 2024 https://doi.org10.4018/979-8-3693-5528-2.ch01
  • Intervention Approaches in Studying the Response to Vitamin D3 Supplementation- Carlberg- July 2023 FREE PDF
  • Methylation of the Vitamin D Receptor Gene in Human Disorders - Dec 2023 FREE PDF
  • Vitamin D and Aging: Central Role of Immunocompetence- Carlberg - Jan 2024 FREE PDF

VitaminDWiki - Response to Vitamin D - many studies 149+

VitaminDWiki - Vitamin D Receptor activation can be increased in 14 ways

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin, intense exercise, Butyrate   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 14 known VDR activators

VitaminDWiki – The Vitamin D Receptor is associated with many health problems __

530 studies in Vitamin D Receptor category

Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells

See also: 48 studies in the Resveratrol category

It appears that 30% of the population have a poor VDR (40% of the Obese )
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems

Health problems include: Autoimmune (19 studies), Breast Cancer (24 studies), Colon Cancer (13 studies), Cardiovascular (23 studies), Cognition (16 studies), Diabetes (24 studies), Hypertension (9 studies), Infant (22 studies), Lupus (6 studies), Metabolic Syndrome (4 studies), Mortality (4 studies), Multiple Sclerosis (14 studies), Obesity (17 studies), Pregnancy (24 studies), Rheumatoid Arthritis (10 studies), TB (8 studies), VIRUS (37 studies),   Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation

55 health problems associated with poor VDR


A poor VDR is associated with the risk of 55 health problems  click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023  click here for details
Some health problem, such as Breast Cancer reduce the VDR

VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR

How to increase VDR activation


Compensate for poor VDR by increasing one or more:

IncreasingIncreases
1) Vitamin D supplement  Sun
Ultraviolet -B		 Vitamin D in the blood
and thus in the cells
2) MagnesiumVitamin D in the blood
 AND in the cells
3) Omega-3 Vitamin D in the cells
4) Resveratrol Vitamin D Receptor
5) Intense exercise Vitamin D Receptor
6) Get prescription for VDR activator
   paricalcitol, maxacalcitol?		Vitamin D Receptor
7) Quercetin (flavonoid) Vitamin D Receptor
8) Zinc is in the VDRVitamin D Receptor
9) BoronVitamin D Receptor ?,
etc
10) Essential oils e.g. ginger, curcuminVitamin D Receptor
11) ProgesteroneVitamin D Receptor
12) Infrequent high concentration Vitamin D
Increases the concentration gradient		Vitamin D Receptor
13) Sulfroaphane and perhaps sulfurVitamin D Receptor
14) Butyrate especially gutVitamin D Receptor
15) BerberineVitamin D Receptor

Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above

Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR

VitaminDWiki – Vitamin D Receptor category:

530 studies in Vitamin D Receptor category

Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems
A poor VDR restricts Vitamin D from getting in the cells

See also: 48 studies in the Resveratrol category

It appears that 30% of the population have a poor VDR (40% of the Obese )
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems

Health problems include: Autoimmune (19 studies), Breast Cancer (24 studies), Colon Cancer (13 studies), Cardiovascular (23 studies), Cognition (16 studies), Diabetes (24 studies), Hypertension (9 studies), Infant (22 studies), Lupus (6 studies), Metabolic Syndrome (4 studies), Mortality (4 studies), Multiple Sclerosis (14 studies), Obesity (17 studies), Pregnancy (24 studies), Rheumatoid Arthritis (10 studies), TB (8 studies), VIRUS (37 studies),   Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation

55 health problems associated with poor VDR


A poor VDR is associated with the risk of 55 health problems  click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023  click here for details
Some health problem, such as Breast Cancer reduce the VDR

VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR

How to increase VDR activation


Compensate for poor VDR by increasing one or more:

IncreasingIncreases
1) Vitamin D supplement  Sun
Ultraviolet -B		 Vitamin D in the blood
and thus in the cells
2) MagnesiumVitamin D in the blood
 AND in the cells
3) Omega-3 Vitamin D in the cells
4) Resveratrol Vitamin D Receptor
5) Intense exercise Vitamin D Receptor
6) Get prescription for VDR activator
   paricalcitol, maxacalcitol?		Vitamin D Receptor
7) Quercetin (flavonoid) Vitamin D Receptor
8) Zinc is in the VDRVitamin D Receptor
9) BoronVitamin D Receptor ?,
etc
10) Essential oils e.g. ginger, curcuminVitamin D Receptor
11) ProgesteroneVitamin D Receptor
12) Infrequent high concentration Vitamin D
Increases the concentration gradient		Vitamin D Receptor
13) Sulfroaphane and perhaps sulfurVitamin D Receptor
14) Butyrate especially gutVitamin D Receptor
15) BerberineVitamin D Receptor

Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above

Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR

Increased risk of diseases if poor VDR

Increased risk associated with a poor Vitamin D Receptor
   Note: Some diseases reduce VDR activation
those with a * are known to decrease activation

Risk
increase		Health Problem
50Lyme Disease *
28Leprosy - another says 3X
15Chronic Heart Failure
15Temporary hair loss
14.7Childhood solid cancers
14Hand, Foot, and Mouth disease
13Sepsis
12COVID Death
11Metabolic Syndrome
9.6Chronic Periodontitis
   and smoke
8Juvenile Rheumatoid Arthritis
8.0Preterm birth
7.6Crohn's disease
7.5Respiratory Tract Infections
7.0Lung Cancer
5.8Low back pain in athletes
5 Respiratory Distress in preemies
5Ulcerative Colitis
5Coronary Artery Disease
5Asthma Child see also 1.3, 2.0 and 3.7
4.6Breast Cancer * 16.9 X another study
4.3Severe COVID in kids
4.1Vitiligo
4Liver Cirhosis
4Polycystic ovary syndrome
3.8Lupus
3.6 Pneumonia - children
3.3 Pre-term birth
3.1 Colon Cancer survival
3 Multiple Sclerosis
3Dengue
3 Waist size
3 Ischemic Stroke
3Alzheimer’s
9X in women
3Parkinson’s
3Gestational Diabetes
2.9Hand, Foot, Mouth Disease
2.8Osteoporosis & COPD
2.7Gastric Cancer
2.6Lupus in children
2.5 Lumbar Disc Degeneration
2.4Lung Cancer
2.3Cardio
2.3Autism
2.2Juvenile idiopathic arthritis
2.1Adolescent idiopathic scoliosis in Asians
2Obesity
2Diabetic Retinopathy
2Parkinson's
2 Wheezing/Asthma see also 5X
2 Melanoma   Non-melanoma Skin Cancers
2Myopia
2Preeclampsia
1.9Uterine Fibroids
1.9Early tooth decay
1.8Diabetic nephropathy
1.8Sleep Apnea
1.6Diabetes - Type I
1.6Prostate Cancer while black
1.5 Diabetes -Type II
1.5Gout
1.5Pertussis
1.5Obesity
1.4Graves Disease
1.4 Rheumatoid arthritis
1.3Hypertension
1.3Childhood asthma see also 5X
1.3Psoriasis in Caucasians
1.3Tuberculosis

VitaminDWiki – Genetics category contains

343 articles in the Genetics category

see also

Vitamin D blood test misses a lot
in Visio for 2023

  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
  • Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells rather than blood was feasible (2017 personal communication)   Commercially available 2019
    • However, test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
        especially if it is one of 51+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
    3) DNA and VDR tests - 120 to 200 dollars $100 to $250
    4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
       Genes are good, have enough Magnesium, etc.
    5) Back Pain
       probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
      • The founder of VitaminDWiki took action with clues #3&5
Vitamin D - A master example of nutrigenomics – April 2023        
11851 visitors, last modified 14 Oct, 2024,
(Cached) Printer Friendly Follow this page for updates
Page actions
Refresh Print
Edit Files 2

Attached files

ID Name Comment Uploaded Size Downloads
19441 VDR Gene expression.jpg admin 06 Apr, 2023 96.54 Kb 271
19440 master example of nutrigenomics_CompressPdf.pdf admin 06 Apr, 2023 1.57 Mb 125