Vitamin D Found to Influence more than 200 Genes

by Kayt Sukel

December 1, 2010

In the past few years, a deficiency in Vitamin D levels has been linked to a host of diseases from cardiovascular disease to cancer, but some scientists wondered if these associations were simply epidemiological artifact—a result of the analysis, not the substance. But researchers at the University of Oxford and the Wellcome Trust Centre for Human Genetics have now demonstrated that Vitamin D has direct influence on over 200 genes, including many implicated in disease. They published their results in the Aug. 24 issue of Genome Research.

Multiple Sclerosis (MS) and Vitamin D

It’s long been known that MS, a devastating autoimmune disorder, is somehow linked to light levels, says Sreeram Ramagopalan, an author on the paper from the Wellcome Trust Centre.

“Years and years ago, epidemiologists noticed that more individuals with MS were born in May in the Southern Hemisphere and November in the Northern Hemisphere. Winter's lack of light played a role,” he says. “It made us wonder if low Vitamin D levels in utero had something to do with the later development of MS.”

George Ebers, lead author of the present study, and his colleagues demonstrated a few years ago that the main gene region susceptible to MS is regulated by Vitamin D. They then wondered how far reaching the vitamin’s influence might be.

“Vitamin D has not just been linked to MS , it’s also involved with other auto-immune diseases and may play a role in cancer,” he says. “It seems improbable at first glance. It seems very unlikely that Vitamin D can be related to all these things. But surprisingly, many of these diseases are somehow connected.”

Mapping Vitamin D Receptor Sites

Ebers, Ramagopalan, and colleagues used a new DNA sequencing technology to map Vitamin D receptor binding sites across the genome. They hoped to identify genes of interest that responded to Vitamin D and determine whether the hormone could increase or decrease the protein production of those genes. ('Vitamin D' is not really a vitamin but a hormone, since most of it is produced by our body as the result of exposing our skin to the sun.)

The group found more than 2,700 genes to which Vitamin D can bind. But more importantly, they found more than 200 genes that were actively up- or down-regulated by the hormone, including genes linked to MS, Crohn’s disease, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus (more commonly known as lupus), and colorectal cancer.

“This paper shows what many of us have thought about Vitamin D for a long time,” says Bruce Hollis, a scientist at The Medical University of South Carolina. “I’ve heard others say, ‘Oh, this is all esoteric. Vitamin D can’t possibly be involved with this many disease processes.’ But this paper shows them to be wrong.”

Anthony Norman, a biochemist at the University of California Riverside who has been studying Vitamin D for more than four decades, says this paper is a true breakthrough. “These results don’t surprise me—I fully expected something like this,” he says. “And with it having such a widespread effect, it shows the implications for health is much more urgent than what many others have thought.” 

Paula Bickford, a researcher at the University of South Florida and co-author of a Cerebrum article published last year on Vitamin D, says that this research should be a call to action to doctors to pay more attention to deficient Vitamin D levels in their patients.

“Vitamin D seems to have a key link to regulating genes involved in a wide range of disease processes,” she says. “If you have a deficiency, you are more at risk to develop diseases like MS or cancer. Physicians should be making sure patients are aware of it and are keeping up the necessary levels.”

But just what a necessary level is as well as how to maintain it remains somewhat controversial. Some doctors suggest that 15 minutes of sunlight exposure per day could make a world of difference.  But given skin cancer rates, others think the benefit wouldn't outweigh the risks. Both the medical community and the Food and Drug Administration are debating whether to fortify more foods with Vitamin D and what amount should be recommended for daily supplementation.

“It’s interesting just how many diseases have been associated with a lack of Vitamin D. But there are still a lot of unanswered questions,” says Marjorie McCullough, the strategic director of nutritional epidemiology at the American Cancer Society. “What’s the optimal blood level to avoid some of these disease outcomes and yet still be safe? Is it better to get those levels through supplementation or direct sunlight? We don’t know. And we really need to find out.”