Risk genes for multiple sclerosis uncovered

A large-scale study into the human genome – our DNA code - has uncovered new genetic variations associated with multiple sclerosis (MS), findings that suggest a possible link between MS and other autoimmune diseases. The study, led by an international consortium of clinical scientists and genomics experts, is the first comprehensive study investigating the genetic basis of MS.

This study confirmed that immune system genes are altered in people diagnosed with MS and pointed to potential mechanisms of the disease. Findings appear in the online edition of the New England Journal of Medicine.

The researchers gathered 931 sets of DNA samples from people with MS and their parents, of which 455 were recruited in the UK by Professor Alastair Compston and is team at the University School of Clinical Medicine in Cambridge. They looked for small variations in DNA that were more commonly inherited by people with MS compared to samples from people without the condition. They confirmed the findings with other sets of families, resulting in a final analysis of more than 12,000 people.

MS arises from a combination of genetic and environmental factors. Scientists believe that a host of genetic variations may contribute to a person’s susceptibility. The only genetic link for MS previously identified using other techniques is in the major histocompatibility complex (MHC), a large cluster of genes responsible for many immune functions, including preventing the body’s immune cells from attacking its own tissues.

This study confirms the MHC link and has also uncovered two new regions of the genome associated with MS. These regions do not cause MS, and are found in 90 per cent of the general population. However they can contribute to the likelihood that someone might develop MS.

One of the regions found contains a gene called the IL-2 receptor, which has also been linked to two other autoimmune diseases, type 1 diabetes and autoimmune thyroid disease. Another region harbours a gene called the IL-7 receptor, which helps to control the activity of a class of immune cells called ‘regulatory T–cells’. Two papers appearing simultaneously in Nature Genetics confirm this finding. “I believe that this receptor and its interaction with regulatory T-cells will now become a major focus of research on MS,” says Stephen Hauser, professor of neurology at University of California San Francisco, and one of the authors on the paper.

Although he pointed out the link between the IL-2 receptor and MS still needs to be confirmed, Professor Gavin Giovannoni, The Institute of Cell and Molecular Science, Barts and the London NHS Trust, said ‘Importantly, both the MHC and IL-7-receptor are involved in controlling the immune response and increase the likelihood that MS is an autoimmune disease. The million dollar question is how these genes interact with each other and the environmental factors linked to MS to cause the disease.’

One of the most encouraging outcomes of this current genomic study,” says Dr John Richert, Executive Vice President, Research & Clinical Programs, National MS Society, “is that it is helping us to pin point genes that may elevate the risk of developing MS and other autoimmune diseases pointing the way to new areas of research and therapeutic targets to both treat and eventually prevent these diseases.”

It is hoped future studies will involve collecting larger numbers of samples and examining more DNA sequences, which will allow scientists to identify subtler variations that contribute to the condition. “This study illustrates the power of collaboration”, added author Adrian Ivinson, Director of the Harvard Center for Neurodegeneration and Repair. “Individually, none of us could have completed a study of this scale and complexity. But using a Collaborative Research Award from the National MS Society we formed a truly effective international consortium that was able to deliver the most exhaustive search for MS risk factors ever published. In an effort to see the work extended, we are now committed to making the entire data set available to MS researchers worldwide.”
http://www.mssociety.org.uk/research/news_in_research/research_news/risk_genes_for_m.html