Vitamin D-related gene changes tied to movement symptoms in MS
Study examines changes in the vitamin D receptor gene in 200 people with MS
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Certain variants in the vitamin D receptor gene were linked to motor symptoms and spinal cord lesions in people with multiple sclerosis, a study found. (Image from iStock)
- Multiple sclerosis is an immune-mediated disease causing inflammation and damage to the central nervous system.
- Specific vitamin D receptor gene variants were linked to motor symptoms and upper spinal cord lesions in a new study.
- Larger studies that examine interactions between genes and environmental factors are needed to confirm these findings and better understand how genetic variants may influence MS symptoms and other disease features.
Small changes in the gene that provides instructions for making the vitamin D receptor (VDR) protein were not individually associated with the risk of multiple sclerosis (MS), but certain variants were linked to motor symptoms and lesions in the upper spinal cord, a new study found.
“In summary, this study contributes to the growing body of evidence supporting the role of vitamin D signaling and host genetic variation in shaping the clinical course of MS,” the researchers wrote.
The study, “Vitamin D receptor gene variants and their association with clinical phenotypes of multiple sclerosis,” was published in Multiple Sclerosis and Related Disorders.
How vitamin D receptor gene variants may be linked to MS
MS is an immune-mediated disease that affects the brain and spinal cord. It causes inflammation and damage to the protective covering of nerve fibers, along with gradual damage to nerve cells.
Low levels of vitamin D have been linked to a higher risk of MS. Vitamin D is found naturally in some foods and is also produced in the skin when exposed to sunlight. Vitamin D is thought to affect immune cell activity mainly through VDR.
Small changes in the VDR gene that affect just one building block of DNA are called single nucleotide variants (SNVs). These changes may affect how the receptor protein works. Three of the most studied SNVs in this gene are called FokI, BsmI, and TaqI. Previous studies have found mixed results about whether these variants are linked to MS. Their possible role in the disease’s symptoms and other features also remains poorly understood.
Researchers in Greece and Cyprus examined whether these three variants were associated with the risk of developing MS, as well as certain symptoms and other features of the disease. They analyzed DNA from 200 adults with MS (72% women) and 265 neurologically healthy adults without autoimmune diseases (49.8% women) who served as a comparison group. All participants reported Southeastern European (Greek) ancestry.
Among those with MS, 59% had sensory symptoms, 30.5% had motor symptoms, and 23.5% reported vision problems.
Overall, the analysis found no statistically significant differences between patients and controls in how common any of the three variants were. An analysis of combinations of genetic variants inherited together, called haplotypes, also found no statistically significant differences between patients and controls.
However, a statistical analysis called logistic regression found a significant interaction between the FokI (CT) and TaqI (AG) genotypes. In that statistical model, the interaction was associated with nearly 16-fold higher odds of MS. The researchers suggested this may reflect an epistatic effect, in which the effect of one genetic variant depends on another.
Gene combinations linked to MS risk and symptoms
Consistent with previous research on MS, being female was also significantly associated with higher odds of MS in the study’s statistical analysis.
After adjusting for age and sex, researchers found that the BsmI GG genotype was significantly more common among patients without lesions on MRI scans of the cervical spinal cord (in the neck). The TaqI (AA) genotype was also more common among patients without these lesions, but the statistical evidence for this association was less conclusive.
After adjusting for age and sex, researchers also found that the BsmI AA and TaqI GG genotypes were significantly more common among MS patients with motor symptoms than among those without. No significant differences were found between patients with and without sensory symptoms.
“Collectively, the study supports the hypothesis that the investigated VDR SNVs possibly play a disease-modifying role rather than being primary MS susceptibility factors,” the scientists wrote.
“In order to confirm and expand on these findings, larger multicenter studies with broader genomic coverage are required,” the team wrote. The team added, “Integrating gene-environment interactions, such as vitamin D status, is also essential for uncovering the functional relevance of these associations.”
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