Multiple sclerosis (MS) is the most common serious neurological disease that affects young adults, wiht about 2.5 million victims worldwide. The disease involves a loss of myelin in brain and spinal cord neural tissues. Myelin is the protective and insulating layer that covers most axons in the mammalian nervous system.
can be caused in part by a particular set of genetic variations in the Major Histocompatibility Complex (MHC), which in turn cause significant neurological effects. There is compelling epidemiological information to suggest that there is also an important environmental factor. The present study makes the argument that vitamin D deficiency, especially during pregnancy and early development, is one such important environmental factor.
The most important genetic effect seems to be a particular allele for a gene on Chromosome 6 that goes by the name DRB1*1501 and adjacent DNA sequences. In the general population (in Britian, where this research was carried out) 1 per 1,000 people are likely to develop MS, but 1 in 300 of those with one copy of this allele and 1 per 100 of those carrying two copies will likely develop the disease.
The present study links DRB1*1501 and vitamin D deficiency. From a press report:
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 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 lead 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.”
You can download and read the original paper here.
Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton S-M, et al. (2009). Expression of the Multiple Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin D PLoS Genet, 5 (2) DOI: 10.1371/journal.pgen.1000369