Rare gene may link MS to vitamin D

By Nathan Gray

- Last updated on GMT

Related tags: Multiple sclerosis, Genetics, Vitamin d

Rare gene may link MS to vitamin D
A rare genetic mutation that results in low vitamin D levels appears to be directly linked to multiple sclerosis, according to new research.

The study – published in Annals of Neurology​ and funded by the MS Society – set out to look for rare genetic changes that might explain clusters of multiple sclerosis (MS) cases observed in some families.

The research team, from Oxford University, UK, sequenced the gene-coding regions of 43 individuals selected from families where four or more people suffered from MS, finding that a rare mutation in the CYP27B1​ gene was the key.

The team then looked at the occurrence of the genetic mutation in a wider group of families where parents were unaffected but the child had MS. They found 35 parents who carried one copy of this variant along with one normal copy; in each of these cases the child with MS had inherited the mutated version of the gene.

“This type of finding has not been seen in any complex disease. The uniform transmission of a variant to offspring with multiple sclerosis is without precedent,”​ said Professor Ebers of the Nuffield Department of Clinical Neurosciences at Oxford University, who led the study.

Study details

The researchers explained that their study is an important advance in research because they have essentially found a small group of people genetically determined to have vitamin D deficiency from birth, and connected this directly to MS.

The researchers said that the likelihood of this gene’s transmission being unconnected to MS is ‘billions to one against’.

“If inheriting the CYP27B1gene variant was unrelated to MS, there would be a 50/50 chance of the child inheriting the variant from their parent,”​ explained Ebers.

“All 35 children inheriting the variant is like flipping a coin 35 times and getting 35 heads, entailing odds of 32 billion to one against. Is this gene variant causative in multiple sclerosis? Pretty much”​ he said.

However he cautioned that since unaffected parents who had a copy of the gene did not have multiple sclerosis, having the rare variant doesn’t mean someone will definitely develop the condition.

Vitamin D

The team led now believe that a role for low levels of vitamin D in MS is now ‘broadly unequivocal’, as the new evidence adds to previous observational studies that have suggested sunshine levels around the globe are linked to MS, and gene studies which have indicated vitamin D is involved in the regulation in key genes associated with the disease.

“Large-scale studies of vitamin D supplements for preventing multiple sclerosis are now strongly warranted. The evidence is strong enough,”​ said professor Ebers.

“It would be important particularly in countries like Scotland and the rest of the UK where sunshine levels are low for large parts of the year. Scotland has the greatest incidence of multiple sclerosis of any country in the world,”​ he said.

Source: Annals of Neurology
Published online ahead of print, doi: 10.1002/ana.22678
Rare variants in the CYP27B1gene associated with multiple sclerosis”
Authors: S.V. Ramagopalan, D.A. Dyment, M.Z. Cader, K.M. Morrison, G. Disanto, et al

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