Multiple Sclerosis Triggered by Gene-Environment Link

Researchers have elucidated the mechanism by which environmental factors such as lack of sunlight act on genes associated with multiple sclerosis.
Multiple Sclerosis Triggered by Gene-Environment Link
5/31/2011
Updated:
9/29/2015
[youtube]qgySDmRRzxY[/youtube] What Is Multiple Sclerosis?Researchers have elucidated the mechanism by which environmental factors such as lack of sunlight act on genes associated with multiple sclerosis (MS), according to an article published online in Nature Communications on 31 May.

MS involves degeneration of the brain and spinal cord as the body’s own immune cells attack the insulating myelin sheaths that surround nerve cells, causing inflammation which leads to often debilitating symptoms such as vision and hearing loss, and neuromuscular problems.

While researchers know the disorder results from both environmental and genetic risk factors, little was understood about the molecular mechanism of this complex interaction.

“Defining how these come together to induce the disease is critical for developing a cure,” says team leader Dr. Michael Demetriou, associate director of the University of California, Irvine Multiple Sclerosis Research Center in a press release. “We’ve taken a giant first step toward understanding this.”

Demetriou and his team studied the effects of various environmental factors, such as metabolism and vitamin D levels (from diet and sunlight exposure), on four genes that produce proteins involved in the disease in blood samples from around 13,000 people.

Previous research by Demetriou and colleagues showed that changes in how sugars are added to these proteins, a process known as N-glycosylation, leads to a disease similar to MS in mice. The scientists realized that a simple sugar and dietary supplement called N-acetylglucosamine (GlcNAc) suppresses N-glycosylation.

The new findings show both vitamin D3 and GlcNAc can reverse the effects of the four genes, leading to normal addition of sugars to proteins.

“This suggests that oral vitamin D3 and GlcNAc may serve as the first therapy for MS that directly targets an underlying defect promoting disease,” Demetriou said.

MGAT1, a genetic variant linked to MS, increases or decreases the sugars attached to proteins depending on metabolism, Demetriou said, which could explain why some people with the genetic risk factor develop MS while others do not.

These complex sugars are believed to play a role in other chronic diseases like cancer and diabetes, and could form the basis of an important new field of medicine.