Role of genetics in multiple sclerosis

Dec 10 2007

New research announced this week has found an association between certain genes and the severity of multiple sclerosis (MS).

The results of the study by Prof George Ebers, Chair of Clinical Neurology at the Wellcome Trust Centre for Human Genetics, will be published in the journal Proceedings of the National Academy of Sciences and represent a step forward in the understanding of the role of genetics in MS.

The study involved comparing genes from people with severe MS who used wheelchairs within five years of being diagnosed and people who had no disability 20 years after diagnosis.

It revealed that a particular version of a gene called HLA-DRB1*01 was rare in people with severe MS and suggests it plays a protective role against the more severe progressive course that some can experience with MS.

Dr Laura Bell, Research Communications Officer for the MS Society, said: "This interesting new study shows that particular genetic factors work to modify the progression of MS and provides insight into the processes which occur in MS development, however it is worth noting that MS is not directly inherited and there is no single gene that causes or prevents it. Environmental factors also play an important role in people's susceptibility to developing MS."

Professor Ebers will be speaking about his research at the MS Society's MS Life convention in Manchester on 29 and 30 March, 2008. MS Life is aimed at everyone effected by MS and will include research talks from eminent scientist from across the world.

For more information, see http://www.mssociety.org.uk/convention/index

Background Information (including quote from Prof Ebers)

MS is an extremely variable and unpredictable condition. The course of the condition, the symptoms experienced and the underlying processes occurring can vary considerably from person to person. Some people may experience occasional mild symptoms, while others may develop severe disability over the course of their MS. The reasons for this are largely unclear.

However, studies in identical twins have provided clues that genetics have an influence on the course and severity of MS as well as people's susceptibility to developing it. For example, in the case of identical twins which both develop MS - there is a 1 in 3 chance that if one identical twin develops MS, the other will too - they often experience a much similar course and severity of MS than non-identical twins or siblings who both develop the condition.

The most important genetic factor associated with the development of MS is a cluster of genes called the HLA (Human Leukocyte Antigen). HLA genes control the immune system's ability to recognise and differentiate between foreign invading cells and the body's own cells.

Previously, certain HLA genes have been shown to increase a person's susceptibility to developing MS. This new study has shown that some forms, or alleles, of HLA genes, at a particular location called HLA-DRB1 play a role in determining MS severity.

Prof George Ebers, Chair of Clinical Neurology at the Wellcome Trust Centre for Human Genetics said: "The interaction between genes, which is already shown to determine susceptibility to MS, now extends to outcome and this finding may focus the search for treatment targets.

"We would like to find a new way to reproduce the effect of this allele as it attenuates progression, something not demonstrated yet for any treatment in the long term."

The study involved investigating genetic differences between people with benign forms of MS and people with severe forms of MS to find if there were specific genes which were more common in either group. The severe group comprised people who used wheelchairs within five years of diagnosis, while the benign group had no disability after 20 years of diagnosis. This showed that one form (or allele) of an HLA gene called HLA-DRB1*01 was much rarer in the severe cases compared to the benign cases of MS, suggesting that its presence protects against the more severe progressive course that some can experience with MS. The results were then confirmed through studies in several groups of people with MS.

It is worth noting that MS is not directly inherited and, unlike some conditions there is no single gene that causes or prevents it. Studies to date suggest that while a combination of some genes make some people more or less susceptible to developing MS, these genes are also common in the general population. Environmental factors also play an important role in people's susceptibility to developing MS.