Vitamin D Binding Protein may affect immune system dendritic cells – March 2022

Transcriptomic analysis reveal the responses of dendritic cells to VDBP

Genes Genomics. 2022 Mar 12. doi: 10.1007/s13258-022-01234-z (behind $40 paywall)
Biwei Cao # 1 2 3, Tao Wen # 1 2 3, Meng Wei 1 2 3, Yuan Xiong 1 2 3, Wan Liu 1 2 3, Li Zhu 1 2 3, Jing Zhou 4

Background: Vitamin D binding protein (VDBP) is an essential plasma carrier protein, which plays possible roles in reproductive health, disease and so on. However, the effects of VDBP on immunity have not been fully studied and the pertinent literatures remain very limited.

Objective: In this study, we introduced the exogenous VDBP into DC2.4 and established a stable DC2.4/VDBP cell line to explore the role of this gene in immunity.

Methods: Dendritic cells (DCs), as the most effective antigen presenting cells (APC) found so far, are directly involved in regulating some innate immunity. In order to evaluate the biological role of VDBP in DCs, we stably overexpressed VDBP in DCs, and conducted Cell Counting Kit-8 (CCK-8 kit) and flow cytometry to detect changes in cell function. CCK-8 kit was used to monitor the viability of DCs after gene overexpression, and flow cytometry was used to detect changes in cell cycle distribution and apoptosis. Subsequently, in order to reveal the mechanism of VDBP regulating DCs, we adopted RNA sequencing (RNA-seq).

Results: CCK-8 results revealed VDBP successfully inhibited viability of DCs. Besides, we found that overexpression of this gene greatly promoted apoptosis and obviously altered the cell cycle distribution of DCs in G1 and G2 phases. Moreover, RNA-seq was carried out and 151 differently expression genes (DEGs) were obtained. In addition, gene differential expression analysis showed that most of them were uniformly enriched in immunity-related pathways.

Conclusion: These results indicated that VDBP greatly repressed proliferation, facilitated apoptosis and changed cell cycle in DCs via altering the expression levels of gene associated with their cellular immunity.

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VitaminDWIKi - Vitamin D Binding Protein category listing has 178 items and the following:

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWIKi - Vitamin D Binding Protein has

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2.5 X	Severe Autism
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility

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VitaminDWIKi - Additional information on Genetics

Gene	# of pages	Location
CYP27A1	449 (Sept 2019)	Liver
*CYP2R1	826 (Sept 2019)	Liver & Tissue
CYP27B1	1430   (Sept 2019)	Kidney & Tissue
CYP24A1	28 in title - May 2022]	excrete excess

• Vitamins regulate some human genes – Feb 2020
• The genetics of vitamin D – Oct 2018
• Does survival of the less fit mean less health (poor genes may be inherited)
  • genes getting worse over generations
• 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
• Vitamin D deficiency is associated with 35 genes, only 7 of are commercially tested – Nov 2019