Abstract
In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual’s response to vitamin D supplementation are not well characterized. Our objective is to describe the changes in the blood transcriptome and explore the potential mechanisms associated with vitamin D3 supplementation in one hundred vitamin D-deficient women who were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing the important blood transcriptomic fingerprints of health and disease states, was performed on pre and post-supplementation blood samples to profile the molecular response to vitamin D3. We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NF-kB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response based on the expression changes of molecules involved in the receptor-mediated intra-cellular signaling pathways and the ensuing predicted effects on cytokine production. Overall, vitamin D3 has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D3 supplementation among individuals in the Middle East as well as other regions.
Highlights
Our study provides a blood transcriptomic resource of the changes that occurred with a three-month weekly course of vitamin D3 supplementation
We summarized our findings in a schematic representing the Differentially expressed gene (DEG) and biological processed altered by vitamin D3 (Figure 6)
Our results indicated that the ubiquitin system may play an important role in mediating vitamin D-dependent regulation of NF-kB
Summary
Vitamin D is well recognized for its functions in the homeostasis of calcium and bone mineralization [1]. In many Arab countries, including Qatar, a high prevalence of vitamin. D deficiency is observed despite ample sunshine [2]. Women cover most of their skin for cultural reasons and are especially affected [3,4,5,6]. A high prevalence of vitamin D deficiency was reported among college-age women in Qatar [7].
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