Breakthrough genetic study further implicates Vitamin D deficiency in MS

*Dr Julia Morahan is the Macquarie Group Foundation MSRA/MS UK Research Fellow based at Oxford.

Evidence for a direct link between Vitamin D deficiency and MS has just been bolstered, with a December publication of exciting new research.

2011 was a dramatic year in MS genetics research, with the results of the largest ever MS genetics experiment published in Nature. It not only identified 57 genes/gene regions affecting MS risk, but also identified specific aspects of the immune response as being pivotal. This study has provided the roadmap for the next few years of genetic research.

The next papers are now starting to appear. In the December edition of the prestigious journal, Annals of Neurology, a UK/Canadian collaboration headed by Prof George Ebers in Oxford and including Dr Julia Morahan (an Australian Research Fellow*), identified the gene from chromosome 12 as the most likely to contribute to MS risk and variants that appear to have a direct link. The gene, called CYP27B1, which activates vitamin D was first identified by the ANZgene collaboration of Australian MS researchers, then confirmed in the 2011 Nature paper.

The UK/Canadian group has now shown that relatively rare variants of this gene, which can cause rickets (a common vitamin D deficiency disease), are nearly 5 times more common in people with MS than healthy controls. Remarkably, in the 35 families where an unaffected parent carried one of these variants of CYP27B1, all affected children inherited the variant, whereas unaffected children usually did not.

There are many other observations that link the Vitamin D deficiency with MS, such as:
• low blood vitamin D levels associated with increased risk of developing MS and increased risk of relapses;
• the latitude effect, where MS risk is highest where vitamin D activation is lowest;
• mouse models of MS showing how vitamin D protects against disease development; and
• another of the 57 genes known to affect MS risk that regulates vitamin D activation.

Vitamin D is known to regulate immune responses through turning genes on or off and many of the 57 genes associated with MS are responsive to vitamin D. This new research reflects the first potential direct genetic link.

The research adds support to proposals for clinical trials using vitamin D to treat MS, and studies to better understand how vitamin D exerts its protective effect, so that better interventions can be designed.

Contributed by A/Prof David Booth
The Hunt Family Foundation MS Senior Research Fellow, Westmead NSW