Abstract
Nutrigenomics may tell us how various nutrients interact with the genome and potentially cause alteration of gene expressions. One nutrient of particular interest is vitamin D, deficiency of which may lead to diseases in various human organ and muscle systems. Decoding the genetics of complex diseases such as autoimmune diseases and/ or cancers associated with the aging process is vital to understand the controversies the beneficial effects of vitamin D supplementation on these diseases. Based on comparative advantages of different model system and recent ChIPseq/ ChIP-chip studies, we previously proposed one novel insightful hypothesis: the genetic regulatory network of Vitamin D Receptor (VDR, homologue of DAF-12 in Caenorhabditis elegans) may act as a common basis in preventing some autoimmune diseases and associated cancers. Further, such diseases may burst up with polygenic genetic mutations and/or variations in that deficiency of vitamin D and lacking of UVB lead to the mal-functional DAF-12/ VDR and lose its buffering potential as a capacitor. The aberrance of environmental factor-induced DAF-12/VDR may counter-intuitively lead to in situ dys-regulation of the expression of an array of its target genes and locallyinduced autoimmunity because of the citrullination of in situ dys-regulated genes, which may be mediated by the VDR-orchestrated autophagy process. Being consistent with the “hygiene hypothesis” and the “danger signals” theory, some VDR/DAF-12 targets may be directly involved in these processes. Several testable predictions will be briefly discussed.
Highlights
Vitamin D acts as a hormone in that it can be produced by our body, but circulates in the bloodstream, and acts on target tissues (Figure 1)
DAF-12/Vitamin D Receptor (VDR) target genes from our ChIP-chip screening showed dozens of overlaps with validated homologues identified in human VDR studies and significantly enriched near genes that are pathologically associated with Autoimmune Diseases (ADs) and cancer [9] (Figure 1), such as human RPC-1/C.elegans rpc-1 [11], FBN1/ fbl-1 [12], SPAG16/WDR5.1, BLK1/src-1 [13], which are involved in
Environmental factor-induced mal-functional DAF-12/VDR may be postulated to cause in situ dys-regulation of expression of an array of its target genes, and leads to locallyinduced autoimmunity, whose citrullination of in situ dys-regulated genes could be largely mediated by a VDR-orchestrated autophagy process and end with autoimmunity
Summary
Vitamin D acts as a hormone in that it can be produced by our body, but circulates in the bloodstream, and acts on target tissues (Figure 1). According to “Occam’s razor”, we prefer a simple theory to a complex one: i.e. the genetic regulatory network of Vitamin D Receptor (VDR) may play a central role in preventing some ADs and associated cancers, and to help understand such controversies [1].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
