Genetic effects of vitamin D studied

Behind the Headlines

Tuesday August 24 2010

The skin produces vitamin D when exposed to sunlight

“Stocking up on vitamin D supplements and enjoying the summer sun could cut the risk of a host of diseases,” reported the Daily Mail.

This news story is based on a study that investigated how vitamin D might influence the risk of certain diseases by affecting the activity of genes. It found that vitamin D binds directly to genes associated with several common autoimmune diseases, including multiple sclerosis, type 1 diabetes, rheumatoid arthritis and colorectal cancer.

Studies of this kind add to our knowledge of the function of vitamin D, and will be used to assess the guidelines for recommended vitamin D intake.

On its own, this study does not provide definitive evidence that lack of vitamin D causes any of these diseases, or that a certain intake of vitamin D will prevent them. It also did not look at how much vitamin D is best for health and whether supplements are as good as natural sources such as diet and the sun.

It is important to get some sunlight for an adequate intake of vitamin D, but this needs to be balanced with the fact that excessive exposure to UV rays increases the risk of skin cancer. Vitamin D can also be found in oily fish, eggs and some fortified foods such as cereals.

 

Where did the story come from?

The study was carried out by researchers from the University of Oxford, the Simon Fraser University in Canada, the University of London, and Barts and the London School of Medicine and Dentistry. It was funded by the Multiple Sclerosis Society of Canada, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the Medical Research Council and the Wellcome Trust. The study was published as an advance online article in the peer-reviewed journal Genome Research.

The study was reported widely and, for the most part, accurately in the media. The Independent explained in detail that the study identified a possible mechanism by which vitamin D binds directly to genes known to be linked to various genetic disorders. The Mail’s report implied that the study shows that boosting levels of vitamin D, potentially through taking supplements, could keep illnesses at bay. However, the study did not look at how differing levels of vitamin D might affect health outcomes, and a clinical trial would be needed for this.

 

What kind of research was this?

The researchers say that a billion people worldwide have vitamin D deficiency due to insufficient sun exposure or inadequate dietary intake. This deficiency has been associated with a greater risk of several diseases including multiple sclerosis, rheumatoid arthritis and type 1 diabetes. How vitamin D might affect the risk of these diseases is not fully understood.

They suggest that one way vitamin D might have an impact on the risk of disease is through altering the activity of certain genes. At the cellular level, vitamin D binds to a protein called vitamin D receptor (VDR), and the resulting combination (called a vitamin D complex) can then bind to specific sites in the DNA called ‘vitamin D response elements’. This can affect the activity of nearby genes.

In this laboratory study, the researchers set out to identify genes that change their activity in response to vitamin D, and where in the DNA the vitamin D complex binds. Their aim was to investigate how vitamin D might affect processes at the cellular level.

 

What did the research involve?

In the laboratory, human cells were exposed to calcitriol, the active form of vitamin D. A technique called ChIP-seq was then used to analyse how the cells had been stimulated at the genetic level.

The researchers isolated and sequenced the fragments of DNA that bound to VDR. These fragments were then mapped to their location in the genome (all the genetic information encoded in the DNA). The researchers were interested in the genes that were near to these sites and that could, potentially, be affected by VDR binding. To identify potential genetic links between vitamin D and disease, the researchers also looked at whether these VDR binding sites were more common (were “enriched”) in areas that contained genetic variations that had been linked to diseases in previous genetic research. These diseases included type I diabetes, Crohn’s disease, multiple sclerosis and other conditions.

The researchers also carried out experiments to determine which genes showed significant changes in their level of activity when the cells were treated with calcitriol.

 

What were the basic results?

The researchers identified 2,776 sites in the DNA that were related to VDR binding, and 229 genes that showed significant changes in their activity in response to vitamin D.

They found that VDR binding sites were more common near genes that have been associated with several common autoimmune diseases. These were:

  • multiple sclerosis (2.2 times more common)
  • type I diabetes (2.9 times more common)
  • Crohn’s disease (3.5 times more common)
  • systemic lupus erythematosus (5.1 times more common)
  • rheumatoid arthritis (2.8 times more common)
  • chronic lymphocytic leukaemia (8.3 times more common)
  • colorectal cancer (4 times more common)

 

How did the researchers interpret the results?

The researchers say their study provides a comprehensive map of VDR binding throughout the human genome. VDR was found to bind to a number of genes associated with autoimmune disease and cancer. Their data, they say, provide “new evidence supporting a role for vitamin D in susceptibility to autoimmune disease through effects on a substantial number of associated genes”.

 

Conclusion

This is a valuable addition to our knowledge of the effects of vitamin D in the cells and how it might affect our risk of certain diseases.

In isolation, this study cannot tell us for certain if lack of vitamin D causes any of the diseases in question, or if a certain intake of vitamin D will prevent them. It also did not look at how much vitamin D is best for health. The question of whether vitamin supplements affect health in the same way as vitamin D from natural sources such as the sun and diet also needs to be addressed.

The effect of vitamin D on health and disease is currently an area of great interest and ongoing research. Studies of this kind add to our knowledge of the function of vitamin D, and will be used to assess the guidelines for recommended vitamin D intake.

It is important to get some sunlight for an adequate intake of vitamin D, but this needs to be balanced with the fact that excessive exposure to UV rays increases the risk of skin cancer. Vitamin D can also be found in oily fish, eggs and some fortified foods such as cereals.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Are we getting enough vitamin D? Daily Express, August 24 2010

MS and arthritis may be linked to lack of sun, say scientists. The Guardian, August 24 2010

Beat cancer with a dose of sunshine. Metro, August 24 2010

Revealed: how vitamin D can protect us from cancer. The Independent, August 24 2010

Sunshine remedy vitamin D keeps diseases at bay. Daily Mail, August 24 2010

 

Links to the science

Ramagopalan SV, Heger A et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Research (www.genome.org), published in advance August 24

Further reading

Straube S, Derry S, Moore RA, McQuay HJ. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database of Systematic Reviews 2010, Issue 1

Avenell A, Gillespie WJ, Gillespie LD, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database of Systematic Reviews 2009, Issue 2

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