Genomic binding sites and biological effects of the vitamin D--VDR complex in multiple sclerosis [corrected]

Environmental factors greatly contribute to the development of complex trait disorders. With the rapid developments in the fields of biotechnology and informatics, the investigations of molecular interactions between host and environmental factors became very detailed and comprehensive. The effects of ultraviolet irradiation, vitamin D synthesis, and receptor binding, and then the involvements of the ligand-receptor complexes in the regulation of cell function received much attention in the last few years and paralleled the accumulation of information concerning genetic determinants of disease susceptibility, transcriptional regulation, cell cycle, mitochondrial biochemistry, and many other elements of cell biology. The importance of vitamin D in contributing to immune regulation, autoimmunity, and susceptibility to multiple sclerosis (MS) is now also recognized, and there are ongoing treatment trials with vitamin D to define whether it is capable of modifying susceptibility to or the course of the disease. This survey aims to capture that part of vitamin D research that helps to better understand the interactions of this molecule and its receptor with the human genome, and the downstream effects of these interactions relevant to immune homeostasis and MS. This relatively narrow scope reveals a very complex molecular network underlying inflammatory demyelination and allows us to hope that a better understanding of the roles of vitamin D and other environmental factors will once make the risk of MS modifiable or, to some degrees, the disease preventable.