Vitamin D Linked to Genetic, Environmental Risk for MS

Allison Gandey

September 26, 2008

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Dr. George Ebers discusses the new study.

September 26, 2008 (Salt Lake City, Utah) — Results from a new study unite the genetic and environmental risks of multiple sclerosis in a disease-specific and gene-environment interaction. Presenting at the American Neurological Association 133rd Annual Meeting, researchers described a link between vitamin D and the pathogenesis of MS.

"There's a connection between the 2 — no question about it," lead investigator George Ebers, MD, from the University of Oxford, in the United Kingdom, told Medscape Neurology & Neurosurgery. "But exactly how it works is not clear yet."

Asked to comment on the work, Emmanuelle Waubant, MD, from the University of California, San Francisco said, "MS is a very heterogeneous disease, and this is an interesting way to look at the factors that predispose people."

She noted, "This study looks at the bigger picture and is the way things should be done. The data provide decent traction and it is an interesting result."

Dr. Ebers and his team examined the major histocompatibility complex (MHC) for deoxyribonucleic acid (DNA) sequences predicted to respond to vitamin-D complexes.

They identified a single sequence, which appeared to be functionally active because it transfected the segment into cell lines and measured functional expression in response to added vitamin D.

Unexpectedly, they found this sequence is haplotype-specific and perhaps evolving in response to selective pressures characterizing the northern migration of European populations.

This solitary MHC vitamin-D–responsive element is strategically located in the promoter region of the class II complex specific to a haplotype associated with MS risk, Dr. Ebers told the meeting.

"These findings further implicate vitamin D in environmentally mediated MS risk," he said.

Sequence Haplotype-Specific

During an interview after the session, Dr. Ebers said his group was surprised by what it found. "Most times you don't find exactly what you are looking for, but in this case, that is exactly what we found. It was as plain as day."

The data suggesting vitamin D is deficient in MS are strong, Dr. Waubant added. "What is unclear is whether or not it also affects the severity of disease."

"Everyone who has examined this from the National Academy of Sciences to the dietary committee of the European Union to a variety of professional organizations all agree pretty much that the amount of vitamin D that people are getting is too low," Dr. Ebers pointed out.

"I know all the experts in the field, and they've sort of voted with their feet," he said. "They're all on vitamin D and their family is on it too. As far as anyone can tell, the amounts in question are harmless, and it's dirt cheap."

Some experts are advocating that given the potential benefit, vitamin D should be widely administered. But others have reservations and are recommending a more cautious approach.

"I'm reluctant to say there's absolutely no risk, because people have been wrong on these things," Dr. Ebers told Medscape Neurology & Neurosurgery. "But I think in this particular case, the evidence has been so strong that it's safe, and all the experts who examine this are comfortable. Plus, many are giving 2000 units a day to pregnant women, so that should be as reassuring as anything."

This study was funded by the Scientific Foundation of the Canadian MS Society and the UK MS Society. The researchers have disclosed no relevant financial relationships.

American Neurological Association 133rd Annual Meeting: Derek Denny-Brown New Member Symposium. Presented September 23, 2008.

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