A study found no genetic risk factors associated with vitamin D in families with a history of multiple sclerosis (MS), suggesting that the link between vitamin D deficiency and MS risk is determined by environmental factors rather than a genetic predisposition.
The study “Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing” was published in the journal Brain and Behavior.
Vitamin D deficiency is increasingly suggested in studies to be a risk factor for developing MS and other autoimmune diseases. As researchers continue to explore whether vitamin D is able to change disease activity, or works as a neuroprotective and myelin repair factor, the debate continues on whether this deficiency has a genetic basis or not.
The hypothesis is that some people may carry genetic variations, or mutations, that impede communication of vitamin D messages to cells, or change the working of its pathway in the brain and spinal cord — the areas damaged by MS.
For this reason, researchers in Spain examined several genes linked to vitamin D signaling within cases of familial MS. They looked at mutations in 94 individuals from 15 families who had at least two members with the disease.
The vitamin D signaling pathway consists of the biological routes by which this vitamin reaches our body — produced in the skin through exposure to sunlight or the small intestine through dietary choices — its activation, conversion to a hormone, uptake by cells, and its biological actions, which range from maintaining calcium and phosphorus levels to regulating immune responses.
Using whole-exome next generation sequencing, the researchers analyzed genes involved at several points of this pathway, including DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3.
By measuring a gene’s variability and comparing it among family members with MS, members with other autoimmune diseases, and those who were healthy, they hoped to identify specific mutations associated with MS.
Researchers found that CUBN and LRP2, which play a role in the entry of vitamin D into cells, were the genes with greater variability across participants.
However, they found no specific relationship between mutations in these two genes, or other genes examined, and MS, either by comparison with unaffected family members or analyzing MS presence across generations.
Some rare variants were also detected in these families. But again, they were not particularly associated with any of the studied groups.
Mutations reported in other studies to be associated with MS were either not detected, or this association was not supported by the data obtained, like variations in CYP27B1 and VDR.
The team argued that such discrepancy in results may be interpreted as familial forms of MS not being influenced by the same genetic alterations linked to vitamin D in sporadic MS, or because the link between vitamin D and MS risk is an environmental factor and not a genetic one.
This possibility is supported by the fact that vitamin D signaling occurs in a variety of cells and tissues, and is influenced by several local factors.
“Although this study does not allow us to confirm either hypothesis, it indeed provides information on the variants found in the vitamin VD [vitamin D] signaling pathway in MS families,” the researchers wrote.
Based on the results, they concluded that vitamin D “could probably play a role in MS more as an environmental factor rather than as a genetic factor.”