Two Studies Report Finding New Genes And Gene Regions That Make People Susceptible To MS

Main Category: Genetics
Also Included In: Multiple Sclerosis
Article Date: 23 Jun 2009 - 4:00 PDT

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Two studies recently published in the journal Nature Genetics report identifying new genes and gene regions that contribute to making people susceptible to developing MS. The findings, by the International Multiple Sclerosis Genetics Consortium and the Australia/New Zealand MS Genetics Consortium, add to a growing list of gene variations linked to MS susceptibility. Identifying all MS genes will likely lead to the development of more effective ways to treat the disease, and open the door to uncovering the cause of MS, which may lead to its prevention.

In an analysis of several genome-wide scans, Philip De Jager, MD, PhD (Brigham & Women's Hospital, Boston) and colleagues in the International Multiple Sclerosis Genetics Consortium (IMSGC, a group of international MS genetic experts created with funding from the National MS Society) report that three genetic variations appear to make people more susceptible to developing MS, including genes that instruct the immune messenger proteins interferon beta and tumor necrosis factor-alpha. (Nature Genetics , Published online: 14 June 2009) This adds to earlier work by the Consortium and other independent investigators, who have now identified scores of genes that may contribute to MS susceptibility. A small number of these have already been validated and many are currently undergoing validation (confirmatory) studies.

Justin Rubio, PhD (Florey Neuroscience Institute, Melbourne) and colleagues in the Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene, supported by MS Research Australia, among others) published the results of a large-scale gene scan that confirmed the association of several genetic variations previously reported to be linked to MS, and identified two loci (regions on the chromosome where genes are located) on Chromosomes 12 and 20 that have been linked to other autoimmune disorders, but not yet to MS. (Nature Genetics , Published online: 14 June 2009)

Background: A major effort has been under way for over a decade to search for the genetic underpinnings of MS - the inherited set of genes that make people susceptible to the unknown triggering factor or factors that lead to the disease. If successful, it would give scientists a roadmap to the cause of MS, as well as to concrete targets for new therapies and possibly even ways to prevent the disease. This painstaking search, involving analysis of the genome (all the genes within the body) and the banking of thousands of DNA samples from patients and family members, was jumpstarted when the IMSGC used cutting-edge gene-chip technology to complete the largest replicated whole genome scan for MS yet in 2007. Now, only two years later, the IMSGC and other groups are taking full advantage of these technologies to identify more and more genes that seem to predispose people to MS.

IMSGC study: This international group pooled together data from three separate genome-wide studies in people with MS, including 895 people with MS genotyped in its original scan. Genetic material from a total of 2,624 people with MS and 7,220 controls without MS were analyzed, and replicated in a sample of 2,215 people with MS and 2,116 controls without MS. The study confirms that three new genetic variations are associated with MS; these variations exist in the genes for interferon regulatory factor 8, tumor necrosis factor receptor superfamily member 1A, and CD6 - immune messenger proteins. The data may indicate that these proteins are involved early on in the development of MS, note the authors. With support from the Wellcome Trust, the National MS Society and other sponsors, the IMSGC is conducting a very large scale genetics project to validate their discoveries and identify all remaining genes that exert significant effects on MS susceptibility.

ANZgene study: The Australian group compared genetic material from 3,874 people with MS and 5,723 people without MS in search of gene variations that appeared to make people more susceptible to developing the disease. They confirmed several gene variations that had been identified in previous studies, including the immune system-related genes CD58, HLA-DR15, IL2RA, and IL7R. The team also identified two loci on Chromosomes 12 and 20 that have been associated with other autoimmune diseases such as rheumatoid arthritis, but not yet with MS. Further study is necessary to determine the exact nature of the genetic variations at work in MS within these loci, but the authors note one interesting candidate -- CYP27B1 on chromosome 12, a gene that instructs vitamin D. There is growing evidence that vitamin D may help protect against the development of MS.

"The pace of advancing genetics technology must by matched by the willingness of researchers to work together worldwide, and of people with MS to participate in genetics research," says John Richert, MD, Executive Vice President of Research & Clinical Programs at the Society. "These studies demonstrate the highest degree of collaboration among people dedicated to a world free of MS. We are fortunate to be witnessing this exciting era in MS genetics."

Source
National MS Society