Thursday, August 26, 2010

Vitamin D Deficiency Linked To Autoimmune Diseases And Cancer

Researchers in the UK and Canada have identified 229 human genes that are influenced by changes in vitamin D levels. Several of these genes are implicated in cancers and to autoimmune diseases such as multiple sclerosis (MS), lupus and rheumatoid arthritis. The findings, published in the journal Genome Research, have important implications for public health, in particular prenatal care.

Advances in DNA (deoxyribonucleic acid) sequencing techniques have made it possible for researchers to study the interactions between proteins and DNA in greater depth and with a higher degree of accuracy than ever before. These powerful tools are helping to shed light on genetic susceptibility to several diseases.

Recent studies have indicated that vitamin D intake could play an important role in susceptibility to MS, type-1 diabetes and rheumatoid arthritis. In addition, it has long been established that vitamin D deficiency, which affects around 1 billion people worldwide, can lead to rickets-induced pelvic contraction and perinatal death. Usually, the deficiency can be avoided by getting enough sunshine or eating oily fish regularly.

The vitamin D receptor (VDR) binds to parts of the human genome, where it influences the activity, or expression, of individual genes. In this latest study, the researchers used a combination of techniques (chromatin immunoprecipitation - ChIP - and massively parallel sequencing) to create a genomic map of where VDR interacts with DNA, influencing how our genes make proteins.

Specifically, the team isolated DNA fragments that were bound to the VDR before and after cells were treated with calcitriol, the active form of vitamin D. They then sequenced the DNA fragments, and mapped these sequences back to the genome.

Ultimately, the researchers were able to identify 2,776 sites of VDR binding and 229 genes whose expression was directly linked to vitamin D. The sites were concentrated near a number of genes that have been associated with susceptibility to MS, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, chronic lymphocytic leukaemia and colorectal cancer. Two of the genes include IRF8 (Interferon regulatory factor 8, associated with MS) and PTPN2 (Tyrosine-protein phosphatase non-receptor type 2, associated with Crohn's disease and type 1 diabetes).

According to Dr Sreeram Ramagopalan of the Wellcome Trust Centre for Human Genetics in the UK, the findings support the hypothesis that vitamin D interacts with genes in the pathogenesis of these diseases, and underscores the serious risks of vitamin D deficiency, especially for individuals who may be genetically predisposed to be sensitive to insufficiency.

'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,' explained Dr Ramagopalan. '

'Our study shows quite dramatically the wide-ranging influence that vitamin D exerts over our health,' added Dr Andreas Heger of the MRC Functional Genomics Unit at Oxford University.

The findings also shed light on changes in skin and hair colour together with optimised vitamin D production as people migrated out of Africa. 'Vitamin D status is potentially one of the most powerful selective pressures on the genome in relatively recent times,' said Professor George Ebers of the Wellcome Trust Centre for Human Genetics. '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.'
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Sources and contacts: Cordis news release
Wellcome Trust: http://www.wellcome.ac.uk/
 Cold Spring Harbor Laboratory: http://www.cshl.edu/ 
Genome Research: http://genome.cshlp.org/

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