Vitamin D Found to Have Effect Over 200 Genes, Emphasizing Ties to Disease

Scientists have mapped the points at which vitamin D interacts with human DNA--and identified over 200 genes that it directly influences.

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 bulk 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 specific cancers and even dementia.

Researchers from the University of Oxford (UK) utilized 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 comprised of the human genetic code.

The researchers discovered 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, and rheumatoid arthritis, and to cancers such as chronic lymphocytic leukemia and colorectal cancer.

The investigators 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,” said Dr. Andreas Heger from the Medical Research Council (MRC) Functional Genomics Unit at Oxford University, one of the lead authors of the study, which was published online in advance of publication August 24, 2010, in the journal Genome Research.

The first author of the article, Dr. Sreeram Ramagopalan, from the Wellcome Trust Center for Human Genetics (Oxford, UK), added, "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 chief 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 earlier suggested that lighter skin color and hair color evolved in populations moving to parts of the globe with less sun to optimize 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, therefore, there are selective pressures in favor of people who are able to produce adequate vitamin D.

This new study supports this theory, having found a significant number of vitamin D receptor-binding sites in regions of the genome with genetic changes more typically found in people of European and Asian descent. It is probable that skin lightening as humans 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,” stated Prof. George Ebers, a 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.”

Related Links:
University of Oxford
Wellcome Trust Center for Human Genetics