Contact: Catriona Silvey
Public Library of Science
Genetic study shows direct link between vitamin D and MS susceptibility 'gene'
Researchers have found evidence that
a direct interaction between vitamin D and a common genetic variant
alters the risk of developing multiple sclerosis (MS). The research,
published on 6 February in the open-access journal
suggests that vitamin D deficiency during pregnancy and the early years
may increase the risk of the offspring developing MS later in life.
is the most common disabling neurological condition affecting young
adults. More than 85,000 people in the UK and 2.5 million worldwide are
thought to suffer from 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 MS risk 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
and from adjacent DNA sequences. Whilst one in 1,000 people in the UK
are likely to develop MS, this number rises to around one in 300
amongst those carrying a single copy of the variant and one in 100 of
those carrying two copies.
Now, in a study funded by the UK's
MS Society, the MS Society of Canada, the Wellcome Trust and the
Medical Research Council, researchers at the University of Oxford and
the University of British Columbia have established a direct
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
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."
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.
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.
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."
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.
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."
The research has been welcomed by Simon Gillespie, Chief Executive of the MS Society (UK).
remarkable results tie together leading theories about the environment,
genes and MS but they are only part of the jigsaw," says Mr Gillespie.
"This discovery opens up new avenues of MS research and future
experiments will help put the pieces together."
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): e1000369. doi:10.1371/journal.pgen.1000369
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