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Rare gene links vitamin D and multiple sclerosis


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8 December 2011 Last updated at 13:15 GMT

Rare gene links vitamin D and multiple sclerosis

A rare genetic variant which causes reduced levels of vitamin D appears to be directly linked to multiple sclerosis, says an Oxford University study.

UK and Canadian scientists identified the mutated gene in 35 parents of a child with MS and, in each case, the child inherited it.

Researchers say this adds weight to suggestions of a link between vitamin D deficiency and MS.

The study is in Annals of Neurology.

Multiple sclerosis is an inflammatory disease of the central nervous system (the brain and spinal cord).

Although the cause of MS is not yet conclusively known, both genetic and environmental factors and their interactions are known to be important.

Oxford University researchers, along with Canadian colleagues at the University of Ottawa, University of British Columbia and McGill University, set out to look for rare genetic changes that could explain strong clustering of MS cases in some families in an existing Canadian study.

They sequenced all the gene-coding regions in the genomes of 43 individuals selected from families with four or more members with MS.

The team compared the DNA changes they found against existing databases, and identified a change in the gene CYP27B1 as being important.

When people inherit two copies of this gene they develop a genetic form of rickets - a disease caused by vitamin D deficiency.

Just one copy of the mutated CYP27B1 gene affects a key enzyme which leads people with it to have lower levels of vitamin D.

Overwhelming odds

The researchers then looked for the rare gene variant in over 3,000 families of unaffected parents with a child with MS.

They found 35 parents who carried one copy of this variant along with one normal copy.

In every one of these 35 cases, the child with MS had inherited the mutated version of the gene.

The likelihood of this gene's transmission being unconnected to the MS is billions to one against, say the researchers.

Prof George Ebers, lead study author at Oxford University, says the odds are overwhelming.

"All 35 children inheriting the variant is like flipping a coin 35 times and getting 35 heads, entailing odds of 32 billion to one against."

He added: "This type of finding has not been seen in any complex disease. The uniform transmission of a variant to offspring with MS is without precedent but there will have been interaction with other factors."

Prof Ebers believes that this new evidence adds to previous observational studies which have suggested that sunshine levels around the globe - the body needs sunshine to generate vitamin D - are linked to MS.

He maintained that there was now enough evidence to carry out large-scale studies of vitamin D supplements for preventing multiple sclerosis.

"It would be important particularly in countries like Scotland and the rest of the UK where sunshine levels are low for large parts of the year. Scotland has the greatest incidence of multiple sclerosis of any country in the world."

Dr Doug Brown, head of biomedical research at the MS Society, called it an important development.

"This shines more light on the potential role of vitamin D deficiency on increasing the risk of developing MS.

"This research is gathering momentum and will be the subject of discussion at an international expert meeting in the USA this month, the outcomes of which will shape future research that will give us the answers we so desperately need about the potential risks and benefit of vitamin D supplementation."

Paul Comer, from the charity MS Trust, said the research strengthened the case for vitamin D being one potential contributory cause of MS.

"Current opinion suggests that a combination of genetic predisposition, environmental factors such as exposure to sunlight and possibly some sort of trigger, such as a viral infection, interact in some way to start the development of MS.

"We welcome any research that clarifies the interplay between these factors. This is another step towards finding ways to reduce the risk of developing MS, but it is likely to be some years yet before we can gauge the significance of vitamin D deficiency to MS."

http://www.bbc.co.uk...health-16086004

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10 August 2011 Last updated at 17:15 GMT

Genetic clues to what triggers MS

By Helen Briggs

Health editor, BBC News website

Around 30 genetic risk factors for developing multiple sclerosis have been discovered by a UK-led team.

It brings to more than 50 the total number of genetic clues to the disease.

The research, published in Nature, will help identify risk factors and perhaps future treatments or even a cure, said the MS Society.

Most of the genes are linked to immunity, backing the idea that the disease is triggered when the immune system turns against itself.

Genes are only part of the story, however, with other factors, such as vitamin D deficiency or a viral infection, thought to play an important role.

The study, carried out by a consortium of international researchers, led by the universities of Oxford and Cambridge, is the largest yet into genes and MS.

It looked at DNA from almost 10,000 MS patients, and more than 15,000 healthy controls.

Twenty three known genetic variations, common in the general population, that give a tiny increase in the risk of getting MS were confirmed, and 29 new ones identified.

Another five are strongly suspected as being involved, bringing the total number of genetic variations associated with MS to 57.

Professor Alistair Compston of the University of Cambridge told the BBC: "This is suddenly a big new number of genes to try to understand.

"80% of the genes that are implicated by the 57 'hits' are immunological. This shouts out that this is an immunological disease at the beginning. This is a very important confirmation."

Around 2.5 million people around the world have MS, 100,000 of them in the UK.

MS is not directly inherited and there is no single gene that causes it. However, research suggests a combination of genes common in the general population make some people more susceptible to developing the neurological disorder.

Other factors are involved, possibly something in the environment, such as an infection or bacteria, or lack of Vitamin D.

Simon Gillespie, Chief Executive of the MS Society said: "By identifying which genes may trigger the development of MS, we can identify potential 'risk factors' and look at new ways of treating, or even preventing, the condition in the future."

Some of the genes found to be important in MS are also implicated in other autoimmune disorders, such as Crohn's disease and Type 1 diabetes, a separate research paper, published in PLoS Genetics, has reported.

http://www.bbc.co.uk/news/health-14475497

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19 April 2011 Last updated at 06:27 GMT

Virus and low sunlight 'raises multiple sclerosis risk'

Low levels of sunlight coupled with glandular fever could increase the risk of developing multiple sclerosis (MS), say researchers.

There are many suspected risk factors for MS and the disease is known to be more common away from the equator.

The study, in Neurology, suggested that low levels of sunlight could affect how the body responds to infection.

The MS Society said the study, based on hospital admissions data in England, added weight to existing evidence.

MS affects about 100,000 people in the UK and is more common in the north of England than in the south.

There are also high levels of both vitamin D deficiency and MS in Scotland, where the MS Society is considering carrying out separate research on a possible link between the two. Around 10,500 people have MS in the country, the highest prevalence of the condition in the world.

With MS the protective layer around nerves, known as the myelin sheath, becomes damaged. Messages from the brain to the rest of the body are disrupted, resulting in difficulty moving, muscle weakness and blurred vision.

Light plus virus

The researchers at the University of Oxford looked at all hospital admissions in England between 1998 and 2005.

They found 56,681 MS cases and 14,621 cases of glandular fever, which is caused by the Epstein-Barr virus.

The study also used data from Nasa on sunlight intensity.

The researchers found that by just analysing sunlight, they could explain 61% of the variation in the number of MS cases across England.

However when they combined the effect of sunlight and glandular fever, 72% of the variation in MS cases could be explained.

Professor George Ebers, from the University of Oxford, said: "It's possible that vitamin D[which is made when the skin is exposed to sunlight] deficiency may lead to an abnormal response to the Epstein-Barr virus.

"More research should be done on whether increasing UVB exposure or using vitamin D supplements and possible treatments or vaccines for the Epstein-Barr virus could lead to fewer cases of MS."

Dr Doug Brown, head of biomedical research at the MS Society, said: "This work adds weight to existing evidence that MS is caused by a number of factors working in combination.

"Vitamin D has been closely studied in recent years and is thought to be a key factor in the development of MS, we look forward to seeing more research dedicated to this important area."

Pam Macfarlane, chief executive of the Multiple Sclerosis Trust, said: "Further research is needed, but being able to accurately predict the risk of getting MS and identifying preventative measures would be another step forward."

Studies in the UK have suggested that the MS prevalence rate in England and Wales is between 100 and 140 per 100,000, about 170 in Northern Ireland and as high as 190 in Scotland. Individual studies in Orkney have recorded rates of over 200.

It has also been noted that areas of high MS prevalence around the world have been settled by Scottish immigrants, according to the MS Trust.

http://www.bbc.co.uk/news/health-13092524

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