Specific Changes in Vitamin D Receptor Protein Linked to MS Risk, Study Suggests

A risk of multiple sclerosis rises in people with specific variations in a protein, called the vitamin D receptor, that affects how this vitamin works and is metabolized in the body, a study drawn from a meta-analysis reports.

Its researchers suggest these variations, or changes within the protein, play a role in MS development.

Their study, “Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis,” was published in the journal BMC Neurology.

Vitamin D is thought to be able to mitigate the risks of being diagnosed with MS. Studies have shown that people with this disease have lower serum vitamin D levels compared to healthy controls.

In the body, vitamin D modulates the immune system by binding to the vitamin D receptor (VDR). Variations in the VDR’s amino acid sequence — the building blocks of proteins — are related to changes in vitamin D’s function and metabolism. 

These VDR variations — known as polymorphisms — may be connected to MS. As a result, many studies have sought to find a link.

However, multiple reviews (meta-analysis) of published studies also reported contradictory results. Some meta-analyses concluded that VDR variation plays a role in MS, while others did not. 

As the strength of any one meta-analysis is based on which particular studies are reviewed, new studies can strengthen the analysis and provide more clarity. 

A research team in Iran, aware of newly published work, conducted a fresh meta-analysis into the possible association between VDR variation and MS risk.

“Since publishing of the last meta-analysis, seven new studies have been founded in electronic databases. Therefore, we conducted a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and susceptibility to MS,” the researchers wrote.

VDR variation was evaluated by a technique called restriction fragment length polymorphisms, in which a group of enzymes, called restriction enzymes, are used to cut the VDR gene into pieces. The resulting fragments are then analyzed. 

These enzymes are sensitive to small changes in the gene sequence, so different VDR variants can be identified by different fragment patterns generated by a specific restriction enzyme. Digestion of the VDR gene with four of such enzymes — BsmI, ApaI, FokI, and TaqI — produced unique fragment patterns, each representing a single VDR variant (named after each enzyme).

The team reviewed a total of 30 studies.

Results showed a significant association between the TaqI variant and MS risk. No elevated overall risk was found in people with BsmI, ApaI, and FokI variants. 

A further analysis based on the geographical location found that in Asian populations the BsmI variant was linked to an increase in MS risk, while ApaI was associated with a lesser risk.

No link was found between any of these variants and MS risk in European populations. 

The Fok1 variant was not associated with a greater disease risk overall, or by geographical region. 

A final statistical analysis found no evidence of publication bias, which can occur if some reviewed studies are selected over others, demonstrating that this meta-analysis was a good representation of the available evidence, the team reported.

“This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility,” its researchers wrote.

However, “future large-scale studies on gene-environment and gene-gene interactions are required to estimate related risk factors, and assist early diagnosis of patients at high risk for MS,” they concluded.