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
- Log in to post comments
Very interesting. Dr. Jasper Rine, UCLA Berkley, was just in town at the U of M discussing his work with Folic Acid and remediation of genetic disease with vitamins. This is the kind of research we need to back for many reasons -- one being that big pharma doesn't have incentives to develop products. The title of Dr. Tine's talk was "Good News from the Human Genome" and this basic research is another example. Thanks Greg.
Someone should push for Soy Milk also getting the Vitamin D added, if it isn't already mandatory....
At first blush, that would also suggest an influence on other autoimmune disorders. (Not that I know a damn thing about the matter; I could easily be FOS.)
Assuming that the notion is not facially silly to anyone with a clue, it would be a relatively easy cross-check.
I've heard about ms & vitamin D (Canada has an unusually high rate of ms & low sunshine), but not that it relates to development in utero and early in life. Thanks for the info.
It's also been linked to leukemia recently ... or I should say drug therapy for it has. I have MS.
This is one of the few posts I've done where I was able to string together more than 3 or 4 words. If you're interested in what it's like to live with it - then here you go .
http://car54.wordpress.com/2008/10/23/i-have-multiple-sclerosis/
there is also an enormous amount of data on vitamin D potential for cancer prevention. The canadian cancer society now recomend everyone takes vitamin D. there is a good website at www.vitaminD3world.com that gives all the data on cancer prevention
Interesting idea about natural selection - genes disable you. MS is caused by Epstein-Barr virus interacting with the immune system.
Unless you never go out into the sun or the shade, (yes UVB bounces off the clouds and hits you to make 'D' there too) Rickets is a nutritional disease, there is no such thing as low vitamin D levels.
The Pharmacology of Vitamin D, Including Fortification Strategies
"During summer, we accumulate vitamin D3 and store it, so that supplies for vitamin D do not become completely depleted during the winter months. Within three days of a dose of vitamin D3, very little of the original vitamin D is detectable in plasma of rats (101) or humans (102). Most vitamin D entering the circulation appears to be excreted unmetabolized into the bile.[...]
If 30,000 years after entering northern Europe natural selection hasn't changed this, as it easilly could, I have to wonder if the reason isn't that the Vitamin D requrements are met, and then some, by North European sunshine.
"If one looks at the system of vitamin D metabolism in Figure 2 from the perspective of a system
designed to control something, it becomes clear that this is a system better designed to cope with an abundance of supply, not a lack of it. The flow of vitamin D toward 25(OH)D is remarkably inefficient, with most bypassing
it. Furthermore, there is no way to correct for deficiency of vitamin D, other than to redirect utilization of 25(OH)D toward 1,25(OH)2D production, which is the pathway most acutely important for life. That is, when supplies of
vitamin D are severely restricted, its metabolism is directed only toward the maintenance of calcium
homeostasis. To expand on the point that the system of vitamin D metabolism is effectively designed for adjusting for higher inputs, not lower inputs, I offer the example of an air-conditioner system. Air conditioners are designed to compensate for excessive heat, but they are a useless way to compensate for a cold environment."
This points towards a natural homeostasis of vitamin D synthesis and storage in northern Europe that has not modified from the one evolved in Africa because it's still dealing with an excess.
Trevor Marshall
"It is thus very difficult to find a population which can be studied in order to ascertain what the level of natural metabolic homeostasis for 25-D might actually be. These studies show a wide variation in levels of 25-D being generated by populations whose diets have probably not yet
been significantly altered by âThe Sunshine Vitamin,â indicating that the unsupplemented metabolic homeostasis is probably in the range 23â60 nmol/L, and that it falls with advancing age."
"When researchers went to an Italian nursing home, they found that 99 of 104 residents had no detectable vitamin D in their blood,"
(Bad news for these people ?)
All of the 104 resident were over 98 years old!
I hate to think how old they would have lived to if they'd kept their vitamin D levels 'normal'.
"The medical community now recommends bloodstream vitamin D levels of at least 75-150 nmol/L, yet these levels are not reached by many tanned, outdoorsy people".
Mad dogs and ....