Vitamin D found to influence over 200 genes, highlighting links to disease
24 August 2010
It is estimated that 1 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 2776 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."
Image: Catching sun. Credit: Impala74 on Flickr
Ramagopalan S et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Gen Res 2010.
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The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.
The MS Society is the UK's largest charity dedicated to supporting everyone living with or affected by MS, providing an award-winning freephone helpline (0808 800 8000), specialist MS nurses and funds around 80 vital MS research projects in the UK.
The University of Oxford’s Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of the University of Oxford's income and expenditure, and two-thirds of its external research income. Oxford's world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.
The Wellcome Trust Centre for Human Genetics was established to undertake research into the genetic basis of common diseases. The scientific objective of the Centre is to explore all aspects of the genetic susceptibility of disease. The Centre houses multi-disciplinary research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology.
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