Genetic Study Shows Direct Link Between Vitamin D and MS Susceptibility Gene
Scientists 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 in PLoS genetics and funded by the MS Society, suggests that vitamin D deficiency during pregnancy and the early years may increase the risk of the offspring developing MS later in life.
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 an 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 condition.
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. While 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 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 DrJulian 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 the DRB1*1501 gene functioning differently in offspring.
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.
"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.
Original publication: Ramagopalan, S et al.; "Expression of the Multiple Sclerosis associated MHC class II allele HLA-DRB1*1501 is Regulated by Vitamin D."; PLoS Genetics 2009. A preview copy of the paper can be downloaded athttp://www.plos.org/press/plge-05-02-knight.pdf.
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