Toronto, February 5/09 - MS Society of Canada funded researchers have found evidence that a direct interaction between vitamin D and a common genetic variant alters the risk of developing multiple sclerosis. The research, to be published on February 6 in the open-access journal PLoS Genetics, suggests that vitamin D deficiency during pregnancy and the early years may increase the risk of the offspring developing MS later in life.
MS is a common inflammatory disease which affects the central nervous system. Between 55,000 and 75,000 Canadians are thought to live with the condition, which results from the loss of nerve fibres and their protective myelin sheath in the brain and spinal cord, causing neurological damage.
The causes of MS are unclear, but it has become evident that both environmental and genetic factors play a role. Previous studies have shown that populations from Northern Europe have increased risk of MS if they live in areas receiving less sunshine. This supports a direct link between deficiency in vitamin D, which is produced in the body through the action of sunlight, and increased risk of developing the disease.
The largest genetic effect by far comes from the region on chromosome six containing the gene variant known as DRB1*1501 and from adjacent DNA sequences.
Now, in a study funded by the MS Society of Canada, the UK MS Society, the Wellcome Trust and the Medical Research Council, researchers at the University of Oxford and the University of British Columbia have established a direct relationship between DRB1*1501 and vitamin D.
The researchers found that proteins activated by vitamin D in the body bind to a particular DNA sequence lying next to the DRB1*1501 variant, in effect switching the gene on.
“In people with the DRB1 variant associated with MS, it seems that vitamin D may play a critical role,” says co-author Dr Julian Knight. “If too little of the vitamin is available, the gene may not function properly."
"We have known for a long time that genes and environment determine MS risk," says Canadian researcher Professor George Ebers, University of Oxford. "Here we show that the main environmental risk candidate – vitamin D – and the main gene region are directly linked and interact."
Professor Ebers and colleagues believe that vitamin D deficiency in mothers or even in a previous generation may lead to altered expression of DRB1*1501 in offspring.
The finding – that the environment interacts directly with the background genetics of MS – complements research recently published in Human Molecular Genetics by Professor Ebers’s group. There, they showed that environment changes to the same gene region can increase the risk of developing MS even further and can be inherited. These so-called "epigenetic effects" are being seen as increasingly important by scientists and there may be ways in which the effects reported in these two papers are related.
"Epigenetics will have important implications, not only for MS, but for other common diseases," says Professor Ebers. "For mothers, taking care of their health during their reproductive years may have beneficial effects on the health of their future children or even grandchildren."
The authors hypothesise that this gene-environment interaction may affect the ability of the thymus, a key component of the immune system, to perform its regular tasks. The thymus produces an army of T cells, which identify invading pathogens, such as bacteria and viruses, and attack and destroy them. There are millions of different T cells, each designed to recognise a specific pathogen, but there is a risk that one type might mistakenly identify one of the body's own cells or proteins.
Ordinarily, the thymus will regulate the T cells and delete those that pose the greatest risk of attacking the body's own cells and proteins. However, the researchers believe that in people who carry the variant, a lack of vitamin D during early life might impair the ability of the thymus to delete these T cells, which then go on to attack the body, leading to a loss of myelin on the nerve fibres.
"Our study implies that taking vitamin D supplements during pregnancy and the early years may reduce the risk of a child developing MS in later life," says co-author Dr. Sreeram Ramagopalan. "Vitamin D is a safe and relatively cheap supplement with substantial potential health benefits. There is accumulating evidence that it can reduce the risk of developing cancer and offer protection from other autoimmune diseases."
“This research represents an important development in our understanding of the cause of MS,” says Dr. Paul O’Connor, national scientific and medical advisor for the Multiple Sclerosis Society of Canada and a neurologist at St. Michael’s Hospital in Toronto.
"The evidence implicating vitamin D in MS susceptibility continues to mount," Dr. O’Connor continues. “Vitamin D insufficiency is emerging as a key factor of MS in both children and adults. This finding links important work in two streams of research and illustrates the important role Canada is playing in understanding a very complex disease.”
Dr. O’Connor cautions that the study does not provide guidelines on vitamin D dosage and that any decisions on treatment or supplementation should be made in consultation with a trained physician.
For more information:
Stewart Wong
National Senior Manager, Media and Public Relations
Multiple Sclerosis Society of Canada
Telephone: 416-967-3025
Cell: 416-575-3025
E-mail: stewart.wong@mssociety.ca