Multiple sclerosis (MS) is a common inflammatory disease that leads to the destruction of the insulating coating that surrounds nerves in the brain and spinal cord. Without this insulation, the electrical impulses the nerves are supposed to carry between the brain and rest of the body get confused or lost along the way, leading to a loss of control of a variety of bodily functions.
Genetic factors, especially variants in immune system genes, are known to play a part in MS. But environment is important too. Most striking is the influence of geography. Increasing distance from the equator is associated with higher prevalence of MS. Sunlight, and specifically its role in generating active vitamin D in the body, has been proposed to be the reason for this effect. The exact role of vitamin D in the disease, however, has not been shown.
New research, published online today in the journal PLoS Genetics, shows a direct connection between vitamin D and the strongest genetic risk factor for MS found so far. These findings suggest that simply taking a supplement during pregnancy and childhood could prevent this disabling disease from developing.
In laboratory experiments, Sreeram Ramagopalan and colleagues from the University of Oxford and the University of British Columbia showed that a variant of the HLA-DRB1 gene called HLA-DRB1*1501 is turned on by vitamin D. Other versions of the HLA-DRB1 gene were not responsive to the vitamin. The researchers did not address what might be responsible for turning these versions on.
In people with European ancestry, each copy of the HLA-DRB1*1501 variant increases the odds of developing MS by about two times compared to someone with no copies. About 40% of this population has at least one copy.
(23andMe customers can check their data for HLA-DRB1*1501 in the Multiple Sclerosis research report.)
The researchers think that in people with the HLA-DRB1*1501 variant, vitamin D deficiency prevents the gene from being turned on during development in utero and in the early years of childhood, when it and other genes like it are involved in training the immune system to distinguish between the body’s own tissues and foreign invaders such as bacteria and viruses. Immune cells that have failed this basic training but nonetheless been released into the circulation are thought to be behind the nerve cell destruction seen in MS.
According to the authors, the idea that it’s not just vitamin D, but when you get it, is supported by data on MS among people who have migrated from sunny low-risk regions such as the Caribbean to regions with low sunlight such as the U.K., where the risk for the disease is much higher.
“Immigrants who migrate before adolescence acquire the risk of their new country, while those who migrate after retain the risk of their home country,” the authors write.
“This study provides more direct support for the already strong epidemiological evidence implicating sunlight and vitamin D in the determination of MS risk. Given that a high frequency of vitamin D insufficiency in the general population has been observed, our data support the case for supplementation during critical time periods to reduce the prevalence of this devastating disease,” the authors conclude.