Vitamin D found to influence over 200 genes, highlighting links to disease

August 23, 2010, Cold Spring Harbor Laboratory

The extent to which vitamin D deficiency may increase susceptibility to a wide range of diseases is dramatically highlighted in research published today. Scientists have mapped the points at which vitamin D interacts with our DNA - and identified over two hundred genes that it directly influences. The results are published today in the journal Genome Research.

It is estimated that one billion people worldwide do not have sufficient vitamin D. This deficiency is thought to be largely due to insufficient exposure to the sun and in some cases to poor diet. As well as being a well-known risk factor for rickets, there is a growing body of evidence that vitamin D deficiency also increases an individual's susceptibility to autoimmune conditions such as multiple sclerosis (MS), rheumatoid arthritis and type 1 diabetes, as well as certain cancers and even dementia.

Now, in a study whose funders include the Medical Research Council (MRC), the MS Society, the Wellcome Trust and the MS Society of Canada, researchers at the University of Oxford have shown the extent to which vitamin D interacts with our DNA. They used new DNA sequencing technology to create a map of vitamin D receptor binding across the genome. The vitamin D receptor is a protein activated by vitamin D, which attaches itself to DNA and thus influences what proteins are made from our genetic code.

The researchers found 2,776 binding sites for the vitamin D receptor along the length of the genome. These were unusually concentrated near a number of genes associated with susceptibility to autoimmune conditions such as MS, Crohn's disease, systemic lupus erythematosus (or 'lupus') and rheumatoid arthritis, and to cancers such as chronic lymphocytic leukaemia and colorectal cancer.

They also showed that vitamin D had a significant effect on the activity of 229 genes including IRF8, previously associated with MS, and PTPN2, associated with Crohn's disease and type 1 diabetes.

"Our study shows quite dramatically the wide-ranging influence that vitamin D exerts over our health," says Dr Andreas Heger from the MRC Functional Genomics Unit at Oxford, one of the lead authors of the study.

The first author of the paper, Dr Sreeram Ramagopalan from the Wellcome Trust Centre for Human Genetics, adds: "There is now evidence supporting a role for vitamin D in susceptibility to a host of diseases. Vitamin D supplements during pregnancy and the early years could have a beneficial effect on a child's health in later life. Some countries such as France have instituted this as a routine public health measure."

The main source of vitamin D in the body comes from exposing the skin to sunlight, although a diet of oily fish can provide some of the vitamin. Research has previously suggested that lighter skin colour and hair colour evolved in populations moving to parts of the globe with less sun to optimise production of vitamin D in the body. A lack of vitamin D can affect bone development, leading to rickets; in pregnant mothers, poor bone health can be fatal to both mother and child at birth, hence there are selective pressures in favour of people who are able to produce adequate vitamin D.

This new study supports this hypothesis, having found a significant number of vitamin D receptor binding sites in regions of the genome with genetic changes more commonly found in people of European and Asian descent. It is probable that skin lightening as we migrated out of Africa resulted from the necessity to be able to make more vitamin D and prevent rickets: vitamin D deficiency led to pelvic contraction resulting in increased risk of fatality of both mother and unborn child, effectively ending maternal lineages unable to find ways of increasing availability of the vitamin.

"Vitamin D status is potentially one of the most powerful selective pressures on the genome in relatively recent times," says Professor George Ebers, Action Medical Research Professor of Clinical Neurology and one of the senior authors of the paper. "Our study appears to support this interpretation and it may be we have not had enough time to make all the adaptations we have needed to cope with our northern circumstances."

Explore further: Study helps clarify role of vitamin D in cancer therapy

More information: Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton S, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC. A ChIP-seq-defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res doi:10.1101/gr.107920.110

Related Stories

Study helps clarify role of vitamin D in cancer therapy

November 17, 2008
A colon cancer cell isn't a lost cause. Vitamin D can tame the rogue cell by adjusting everything from its gene expression to its cytoskeleton. In the Nov. 17 issue of the Journal of Cell Biology, Ordóñez-Morán et al. ...

Vitamin D may exacerbate autoimmune disease

April 8, 2009
Deficiency in vitamin D has been widely regarded as contributing to autoimmune disease, but a review appearing in Autoimmunity Reviews explains that low levels of vitamin D in patients with autoimmune disease may be a result ...

Low vitamin D levels may be common in otherwise healthy children

July 9, 2007
Many otherwise healthy children and adolescents have low vitamin D levels, which may put them at risk for bone diseases such as rickets. African American children, children above age nine and with low dietary vitamin D intake ...

Variant of vitamin D receptor gene linked to melanoma risk

September 22, 2008
A new analysis indicates an association between a gene involved in vitamin D metabolism and skin cancer. Published in the November 1, 2008 issue of Cancer, a peer-reviewed journal of the American Cancer Society, the study ...

Genome-wide study identifies factors that may affect vitamin D levels

June 10, 2010
An international research consortium has identified four common gene variants that are associated with blood levels of vitamin D and with an increased risk of vitamin D deficiency. The report from the SUNLIGHT consortium ...

Variants of vitamin D receptor linked to increased risk of breast cancer

April 17, 2008
Genetic variations in the body's receptor for vitamin D could increase the risk of breast cancer in postmenopausal women, according to a study published today in the open access journal Breast Cancer Research.

Recommended for you

Study shows DNA methylation related to liver disease among obese patients

July 18, 2018
DNA methylation is a molecular process that helps enable our bodies to repair themselves, fight infection, get rid of environmental toxins, and even to think. But sometimes this process goes awry.

Childhood stress leaves lasting mark on genes

July 18, 2018
Kids who experience severe stress are more likely to develop a host of physical and mental health problems by the time they reach adulthood, including anxiety, depression and mood disorders. But how does early life stress ...

Protein found to be key component in irregularly excited brain cells

July 17, 2018
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor ...

World's largest study on allergic rhinitis reveals new risk genes

July 17, 2018
An international team of scientists led by Helmholtz Zentrum München and University of Copenhagen has presented the largest study so far on allergic rhinitis in the journal Nature Genetics. The data of nearly 900,000 participants ...

New platform poised to be next generation of genetic medicines

July 16, 2018
A City of Hope scientist has discovered a gene-editing technology that could efficiently and accurately correct the genetic defects that underlie certain diseases, positioning the new tool as the basis for the next generation ...

Overcoming a major barrier to developing liquid biopsies

July 16, 2018
The idea of testing blood or urine to find markers that help diagnose or treat disease holds great promise. But as technology has improved to allow researchers to examine tiny fragments of RNA, one major problem has led to ...

12 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

kevinrtrs
1.5 / 5 (8) Aug 24, 2010
The sense I get from the title is that it was deliberately chosen to achieve maximum reading - it's alarmist in that it subtly implies that vitamin D is the CAUSE of diseases, not the LACK of vitamin D.

Other than that it is about time Vitamin D was raised to fully occupy the radar screen because air pollution is one of the major causes of depletion of Vit. D. We're probably going to experience an exponential increase in the price of Vit D. supplements from hereon out. Typical cash in on the health trend mentality [though one could also subscribe to supply and demand...].

moj85
4 / 5 (4) Aug 24, 2010
kevintrs: and yet you can get Vitamin D from the sun.. so how is air pollution causing (directly) the depletion of Vit. D?

Just stand outside for 5 minutes a day and you're all set!
Skeptic_Heretic
3 / 5 (2) Aug 24, 2010
Other than that it is about time Vitamin D was raised to fully occupy the radar screen because air pollution is one of the major causes of depletion of Vit. D.
No, poor diet is the leading cause of vit. D depletion. Most people over the age of 28 no longer produce vit. D from sun exposure due to a multitude of genetic factors and biological vectors due to our extended lifespans.
kevintrs: and yet you can get Vitamin D from the sun.. so how is air pollution causing (directly) the depletion of Vit. D?
He won't answer you so I'll guess he's referring to atmospheric dimming.
freethinking
2 / 5 (4) Aug 24, 2010
SH I disagree with you that poor diet is the leading cause of vit D depletion as I never heard that most people over 28 produce it. Do you have info to back this up?

I have always believed that people should not be afraid of the sun as it is natural and people are designed to be outside, and that there is no need to slather sun screen on. I use sun screen only to prevent burns on myself and kids. Moderation is key to sun exposure.

Skeptic_Heretic
5 / 5 (1) Aug 24, 2010
I can't find the papers I had on the topic. I'll recant until I can find them again. Assertion without evidence is invalid.
dutchman
not rated yet Aug 25, 2010
University of California TV broadcast a whole series on the latest findings in Vit.D research. The main thing I walked away with was: Everyone needs more vit. D. More important: I need more Vit. D.

This is a link to the presentations for on-line viewing:
http://ucsd.tv/se...t=health
fmfbrestel
5 / 5 (1) Aug 30, 2010
"Secosteroids are very similar in structure to steroids except that two of the B-ring carbon atoms (C9 and 10) of the typical four steroid rings are not joined, whereas in steroids they are." -- wikipedia

quit fearmongering, It is not a steriod, it is a substance with a similar structure. However, structural resemblance does not mean diddily to your body's chemical receptors. It is an all or nothing game.
Skeptic_Heretic
5 / 5 (1) Aug 30, 2010
Think carefully before you start supplementing with steroids as they are used medically to supress the immune system.
There are hundreds of types of steroids, almost all of which are created through biosynthesis. The vast majority of steroids have little to no effect on the immune system, and in some cases boost the immune system. You might want to pare down that statement with some more accurate definitions before you're called to the carpet as a loon. Oops, too late. Brestle got you first.
Skeptic_Heretic
5 / 5 (1) Aug 30, 2010
And, I note that you are NOT disputing the fact that "D" is a secosteroid and not a vitamin that the article claims, and that was the point of my post.
If I could draw a Venn diagram one side would have Vitamin, the other would have secosteroid and in the overlap D would lie.
fmfbrestel
not rated yet Aug 31, 2010
right, fixer you're just looking out for the little guy. You're probably an employee of Merk. There is no big business push to promote vitamins, the big money doesn't like this kind of research because they make too much money treating the symptoms.
fmfbrestel
not rated yet Aug 31, 2010
and for the record, secosteroids are NOT steroids. But yeah, Vitamin D can kill you. So can drinking too much water.

But i guess you think that every scientist who has ever published a study is only trying to deceive the masses. And Oxford scientists, well they are the biggest pack of liers out there. Probably are trying to solve for overpopulation by tricking people into maintaining high Vitamin D levels. How devious of them.
fmfbrestel
4 / 5 (1) Aug 31, 2010
Vitamin is not a category of chemical structure. Secosteriod IS a category of chemical structure. Vitamin D fits nicely in both categories without any contradictions. So, no, we aren't disputing that Vitamin D is a secosteriod because it doesnt matter.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.