When Genes Meet the Environment: How Epigenetics Shapes Multiple Sclerosis

Multiple sclerosis (MS) is a complex disease that has puzzled scientists and clinicians for decades. Why do some people develop MS while others—despite carrying similar genetic risk factors—remain healthy? Why does the disease course differ so much among patients? Increasingly, researchers are looking toward epigenetics for answers.

In their influential review, Huynh and Casaccia (2013) brought together evidence showing that MS is not solely the result of genetics or environment, but rather the interaction between the two. Epigenetic mechanisms—changes in how genes are expressed without altering the DNA sequence itself—may serve as the bridge that connects environmental influences with the body’s biological response.

What Is Epigenetics, and Why Does It Matter in MS?
Every cell in our body contains the same DNA, yet cells take on very different roles—neurons transmit signals, immune cells fight pathogens, and oligodendrocytes produce myelin. This diversity arises from epigenetic regulation: chemical modifications to DNA and histone proteins, and the actions of non-coding RNAs.

The three main epigenetic processes are:

DNA methylation – adding methyl groups to DNA, usually silencing genes.

Histone modifications – altering the proteins that package DNA, making genes more or less accessible.

Non-coding RNAs (especially microRNAs) – fine-tuning gene expression post-transcriptionally.

In MS, these mechanisms may help explain why immune cells attack myelin, or why myelin repair fails in the brain.

How the Environment Leaves Its Mark
Epidemiological studies have long hinted that where you live, what you eat, and even when you were born can affect MS risk. For example:

Geography & vitamin D: MS is more common in regions with less sunlight exposure. Low vitamin D—an immune regulator—has been linked to higher risk.

Diet & metabolism: Folate intake influences DNA methylation, while adolescent obesity and high-fat diets may increase susceptibility.

Smoking: Smoking has been tied to DNA methylation changes relevant to immune function.

Epigenetics provides a biological explanation for these environmental effects: they change how genes are switched on or off, tipping the balance toward disease in genetically susceptible individuals. Epigenetic Changes in MS Patients
In Blood
Studies of DNA methylation in immune cells from MS patients have shown subtle, but potentially important, differences. For instance, promoter methylation patterns in some genes can distinguish patients in remission from those in relapse.

MicroRNAs also play a role. Certain miRNAs, like miR-155 and miR-326, are consistently dysregulated in MS. These molecules promote inflammatory T-cell activity and worsen disease in animal models, but silencing them reduces symptoms. Intriguingly, miRNA profiles may even serve as biomarkers for diagnosis or treatment response.

In the Brain
In brain tissue, epigenetic signatures are highly cell-type specific. For oligodendrocytes, too much histone acetylation blocks the production of myelin genes, while histone deacetylation supports myelin repair. But here’s the catch: therapies that broadly inhibit histone deacetylases (HDAC inhibitors) may reduce inflammation yet simultaneously hinder remyelination—a double-edged sword.

Another modification, histone citrullination, is increased in MS brains and linked to instability of myelin proteins. This may make myelin more vulnerable to immune attack.

Implications for Treatment
The insights from epigenetics suggest a future where MS therapy could be personalized. Instead of “one-size-fits-all” treatments, doctors may one day map a patient’s epigenome—identifying which genes are switched on or off in their immune cells and brain—and tailor therapies accordingly.

For example:
Patients with repressive epigenetic marks on vitamin D receptor genes might not respond well to supplementation.

Targeted miRNA therapies could reduce inflammation without interfering with myelin repair.

Drugs that precisely modify histone activity in oligodendrocytes (but not in neurons or T cells) might enhance remyelination.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Huynh, J. L., & Casaccia, P. (2013). Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. The Lancet Neurology, 12(2), 195-206.