Multiple sclerosis (MS) is a debilitating neurological disease affecting over 2 million people worldwide. A number of past studies have provided epidemiological evidence suggesting that low levels of vitamin D are linked to an increased risk of multiple sclerosis (MS). Researchers at Oxford University and the University of British Columbia have now established a link between certain genes associated with MS susceptibility and vitamin D.
The study focused on the HLA-DRB1 gene, which is part of the Major Histocompatability Complex (MHC) of chromosome 6. Variations of this gene have been previously linked to genetic susceptibility to MS in northern Europeans. The researchers set out to establish a connection between this genetic risk and vitamin D. Vitamin D levels have been purported as an environmental factor in the development of MS, and low vitamin D levels, as well as levels of sunlight exposure have been associated with the incidence of MS.
Examination of variants of the HLA-DRB1 gene revealed the presence of a vitamin D response element (VDRE) in the promoter region of the gene. It was found that vitamin D could switch on the expression of the gene by binding to the VDRE. Of particular interest is the fact that the VDRE was found to be present with a very high frequency in the gene variant associated with MS susceptibility (HLA-DRB1*15) and with less frequency in non-MS associated variations.
The authors hypothesize that expression of the HLA-DRB1 gene is involved in the destruction of self-reactive T-cells early in life. T-cells are key immune system cells that attack foreign invaders. However, some T-cells develop a tendency to react to the body’s own proteins as well – these are called “self-reactive” T-cells. If they are not destroyed these cells can turn on the body, and lead to the development of auto-immune disorders like MS.
This study provides very important evidence of a direct association between genetic and environmental risk factors for MS. Not only does this establish a convincing link between vitamin D and MS, but also imparts a greater understanding of the mechanism by which vitamin D can help prevent MS.
Source: Ramagopalan SV et al. Expression of the Multiple Sclerosis-Asscoiated MHC Class II Allele of HLA-DRB1*1501 is Regulated by Vitamin D. PLoS Genetics. 2009; 5(2): e1000369.
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