Tuesday, 24 August 2010

Vitamin D and the genome

New research shows the effect of vitamin D on the genome is widespread and localises to genes and areas of the genome associated with increased susceptibility to MS and other autoimmune diseases. This paper is very important in that it provides a clue to why the effects of vitamin D are so widespread and potentially why vitamin D deficiency is associated with so many different diseases.

Click here for article

Please see the following press releases on the significance of this work:

1. The Guardian
2. The Metro

Sunday, 15 August 2010

MS and Twins

Twin studies were first proposed over a century ago to separate the relative contributions of nature (genes) and nurture (the environment) in determining a trait/disease. Higher concordance (where both twin pairs are affected) rates between genetically identical (monozygotic, MZ) twins versus non identical (dizygotic, DZ) twins provides evidence for genetic factors determining a disease. In MS, about 30% of MZ twins are concordant as compared to about 5% of DZ twins. More MZ twins being concordant as compared to DZ, suggests that genes are involved in MS, but the fact that MZ twins are not 100% concordant means that the environment also plays a role in the cause of MS.

However, given that the average adult has billions of cells and that when DNA is copied between these cells errors can arise, differences in the DNA sequence of MZ twins have been reported. Furthermore, a relatively new field of genetics, called epigenetics, which refers to modifications of DNA that regulate the function of the genome, has also been shown to differ between MZ twins. MZ twins discordant for a disease could actually therefore be explained by genetic or epigenetic differences between twins, but until recently this has not been examined in detail.

Baranzini and colleagues sequenced the genome and epigenome from one pair of MZ twins discordant for MS (http://www.nature.com/nature/journal/v464/n7293/full/nature08990.html). Given that the sequence of the first human genome that was released in 2000 represented 15 years of work and $3 billion. This work represents the future of genetic research as technology has vastly improved meaning that a whole genome can be sequenced in 1 week for $10,000.

So what was found? Comparison of the entire genome and some regions of the epigenome did not find any reproducible difference in DNA sequence between twins, suggesting that as previously thought, the environment plays the most significant role in determining twin concordance for MS.

However, genetic and epigenetic differences between twins are not completely ruled out by this study. Whilst the paper represents a huge effort, there are a number of limitations including the fact that only 3% of the epigenome was investigated. The epidemiology of MS (e.g. more females being affected) implies that epigenetics will be important in the cause of the disease and more work is needed to work out which factors are involved.

Watch this space.

Tuesday, 10 August 2010

The Genetics of CCSVI

A recent study published in BMC Medical Genetics (http://www.biomedcentral.com/1471-2350/11/64) has attempted to study genetic risk factors for CCSVI. The authors investigated
copy number variations (CNVs, segments of DNA that differ between people in terms of number of copies) in the HLA region (the region that confers the biggest MS genetic risk) of 15 patients with CCSVI. The authors found that the number of CNVs correlated with the number of venous malformations a patient had.

This is an interesting study, but needs to be validated in a much larger cohort of patients and healthy controls. Furthermore, it is not yet clear how CNVs in different parts of the HLA region can lead to the same CCSVI phenotype.

Monday, 9 August 2010

Following the sunshine vitamin

This BBC radio show is a great listen. It’s discusses the virtues of Vitamin D, particularly where Britain’s health is concerned. The presenter interviews many leading experts in vitamin D such as Prof. Reinhold Vieth (University of Toronto), Dr. Doug Brown (MS Society) plus many others. It’s a succinct story about the ins and outs of the vitamin and why our low levels of vitamin D are becoming a concern. The benefits of a higher vitamin D status are said to span some 30 diseases (including MS), pregnancy and even sports performance.

As it is difficult to get enough vitamin D from diet alone, many are recommending vitamin D supplementation (vitamin D3), and some are pushing for the fortification of foods.

It’s a half-hour show and good food for thought, so have a listen here: http://www.bbc.co.uk/iplayer/episode/b00t66nr/Food_Programme_01_08_2010/