Low vitamin D has long been a risk factor for developing MS, but how does that tie in with MS risk genes? A team at the Menzies Institute for Medical Research in Tasmania is a step closer to finding out. MS Research Australia funded scientists Professor Bruce Taylor and Professor Heinrich Korner have discovered an intriguing link between control of our genes and vitamin D.
There are thousands of genes in each cell in the human body but each cell doesn’t necessarily use all the genes, and which genes it does use are very tightly controlled. This research shows that vitamin D might affect which genes the cells are using and how much they are using them.
Our genes are interspersed amongst our DNA, and next to the genes in our DNA are short sequences called promoters and enhancers, which as their names suggest have the potential to aid in the making or using of the genes around them. For this to happen they need special proteins within the cells to bind to these sequences and this then tells the cell to carry out those genetic instructions.
Using publicly available DNA data from previous large genetic studies in people with MS and sophisticated computation analysis, the researchers looked at some genetic enhancers, known as ‘super enhancers’, which proteins bind to when vitamin D is present. They refer to them as vitamin D super-enhancers, so in other words, when vitamin D is present, proteins bind to these super-enhancers telling the cell to make the genes in close proximity.
Published in the journal Frontiers in Immunology, the study showed that there was significant overlap between the vitamin D super enhancers and MS risk genes. They identified five MS risk genes that were strongly regulated by vitamin D super-enhancers, that is cells either made far more or less of these genes when vitamin D was present. These genes were involved in a range of functions, including immune response and inflammation in the brain. An additional five genes were identified but these did respond so strongly to the presence of vitamin D.
The team also specifically investigated a particular gene called ZMIZ1 to see if it was controlled by vitamin D super-enhancers. ZMIZ1 is already of interest in MS as it has previously been shown that cells in people with MS produce a very different level of this gene compared to people without MS. The researchers found that the ZMIZ1 gene was regulated by vitamin D super-enhancers.
This study provides a crucial link between vitamin D and genes known to be associated with MS. It provides a connection right at the molecular level of how vitamin D and MS genetic risk factors might interact.