Molecular link between vitamin D deficiency and MS

The vitamin may interact with a gene associated with multiple sclerosis

Scientists are shining some sunlight on the molecular connection between vitamin D deficiency and multiple sclerosis.

A form of vitamin D triggers activity of an immune system gene linked to the disease, researchers from the University of Oxford and the University of British Columbia report in a study published online February 6 in PLoS Genetics.

Epidemiology reports have previously found that the farther people live from the equator, the more likely they are to develop multiple sclerosis. MS is an auto-immune disease in which the body attacks the myelin sheath that protects nerve cells. More than 2.5 million people worldwide have the disease.

People who have multiple sclerosis often have low levels of the vitamin in their blood. But scientists did not know how vitamin D works in the immune system, or how deficiency of the vitamin is connected to the disease. The new study is the first to establish a genetic link between MS and vitamin D.

“It’s certainly teasing away at understanding why someone develops MS to begin with,” says Patricia O’Looney, vice president of biomedical research at the U.S. National Multiple Sclerosis Society in New York City.

Previous genetic studies have shown that people with one variety, or allele, of the HLA-DRB1 gene have a greater chance of getting MS. The gene is located in the major histocompatibility complex on chromosome 6, one of the most variable regions in the human genome. HLA-DRB1 comes in 400 varieties. One of those alleles, designated HLA-DRB1*1501, is the most common variant in Northern Europeans and those who carry the allele have a three times greater risk of developing MS.

Researchers led by George Ebers and Julian Knight, both of the University of Oxford, report in the new study that HLA-DRB1*1501 contains a switch in its control panel that is activated by one form of vitamin D. The switch, called a vitamin D response element, was missing from the control panels of alleles not associated with multiple sclerosis. 

HLA-DRB1 may be important for helping the immune system learn which proteins are normal parts of the body and which signal the presence of a foreign invader. If people with the vitamin D responsive form of the gene don’t get enough vitamin D, the gene may not be properly activated, causing the body to mistakenly attack itself. Based on this idea and other data, the researchers speculate that vitamin D may be important early in the development of the immune system, even while in the womb, so providing vitamin D supplements to pregnant women and infants may help prevent development of MS later.

Ebers says the team is examining other alleles to see whether they also contain the response element and carry a higher risk of MS. Knowing if the two always come together will be important for targeting a treatment and for determining who is at risk of developing the disease.

“The likelihood that [the response element] is going to be important is good,” Ebers says, “but exactly how it works is going to need more work to understand.”

Tina Hesman Saey

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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