SUNDAY, July 29, 2007 (HealthDay News) -- In the most significant genetic breakthrough in multiple sclerosis research in three decades, scientists say they have unearthed a gene that can increase the risk of developing the autoimmune disease by 30 percent.
The gene is only the second genetic risk factor for multiple sclerosis (MS) ever discovered.
The finding of the gene, on chromosome 5, is detailed in two studies in the July 29 online issue of Nature Genetics and confirmed in a third, corresponding study in the New England Journal of Medicine that was released early to coincide with the Nature Genetics report.
"This is the first big step we've taken in 30 years," said Simon Gregory, lead author of the first Nature Genetics paper and a molecular geneticist at Duke University's Center for Human Genetics. "We can start unlocking mechanisms by which the disease is caused and, if we have the mechanisms, we can develop additional treatments. Ultimately, we can start looking for a cure."
"Every time we identify new genes that are associated with increased risk of developing MS, we achieve two things," added Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society, which was a sponsor of the research. "We understand more about the cause of the disease so that eventually we will be able to prevent MS from even occurring. That's a long-term outcome. A shorter-term outcome will be the development of new therapies that are directed at this gene or the gene product so that we will have tremendous direct benefit to people with MS overly a relatively shorter period of time."
MS is a disease of the central nervous system in which the body attacks and destroys the myelin, or insulation, covering nerve fibers. The disease most often attacks people under the age of 55, and symptoms can range from mild muscle weakness to partial or total paralysis. MS is widely believed to occur as a result of both genetic and environmental factors.
Between 1972 and 1975, researchers found that a variant of the human leukocyte antigen (HLA-DRB1) increased the odds of getting MS up to fourfold. This was the only previously discovered MS gene, and it was located in an area of chromosome 6 involved in regulation of the immune system.
"It's like a puzzle. We'd had this corner piece sitting up there and it's been like that since the 70s," said Margaret Pericak-Vance, co-senior author of Gregory's paper and director of the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine. "We know that genetics are important in MS. We knew that if we're really going to figure out how to treat this disease or even prevent it, we needed to figure out what's going on with the genetics. We knew that the immune system obviously was involved, but what were some of these other genes?" she said.
The scientists involved in the current discovery analyzed genetic information from 12,360 people (both with and without MS) using "genomic convergence." This involves using several different independent techniques, then overlapping them to focus in on likely candidate genes.
After years of work, the researchers determined that the interleukin 7 receptor (IL7R) alpha chain gene is associated with MS. The gene is involved with the normal functioning of the immune system.
The researchers involved in the NEJM paper confirmed the findings using "whole genome association," whereby they scanned the entire genome for possible genes.
Because that study took a genome-wide approach, they were able to identify additional genes which, while not achieving statistical significance in this phase of research, do merit further attention. "They identified a couple of other candidate genes," Gregory said. "The next big step is to figure out how all these genes work together."
This could be just the beginning to unraveling the genetics of MS, experts said.
"What this tells us that now we have the technology to be able to identify genes that provide only a modest increase in the genetic risk of developing MS," Richert said. "We are going to figure out in relatively short order the genetic complements that set the inherited stage for developing MS."
"This is getting us into another pathway. It allows us to ask new questions, new relevant questions that we didn't know to ask before," Pericak-Vance said. "Now we have to figure how they're involved, if other genes in the pathway are involved."
But genetics are just part of the picture.
"We also have environmental influences as well," Gregory said. "Genetics will take us a certain distance, but there will be other environmental factors that contribute to developing MS."
More information
Visit the National Multiple Sclerosis Society for more on this disease.
