Secret codes of MS cracked
July 30, 2007
INVESTIGATORS have reported the biggest breakthrough in decades into the genetic drivers for multiple sclerosis, identifying two genes that each boost the risk of developing the disease by up to 30 per cent.
In MS, the immune system attacks myelin, the fatty sheath that protects the cells of the central nervous system, rather like plastic insulation protects electrical cables.
As a result, "short circuits" occur in the body's messaging system, because nerve signals get slowed or blocked. This leads to difficulties in movement and co-ordination, muscle weakness, cognitive impairment, slurred speech and vision problems.
Until now, investigations of the human genome have turned up only a cluster of variants of genes on Chromosome 6, in the so-called Major Histocompatibility Complex, which regulates the immune system.
But these genes were identified in the mid-1970s, leaving frustrated doctors to hunt for other culprits in the complex cascade of processes involved in MS. The new suspects play a role in guiding key immune cells, called T cells, which patrol the body for intruders.
They carry the name of interleukin-7 receptor alpha, or IL7R-alpha, located on Chromosome 5, and interleukin-2 receptor alpha (IL2R-alpha) on Chromosome 10, which has previously been associated with Type 1 diabetes. A single change in the genetic code in IL7-R, and two changes in IL2-R create the dangerous variants.
Each variant appears to boost the risk of MS by between 20 and 30 per cent.
"Our finding is very important, because the genetic factors that are already known to be associated with multiple sclerosis only explain less than half of the total genetic basis for the disease," said Simon Gregory, an Australian-born geneticist at Duke University in Durham, North Carolina, who took part in the IL7-R work.
The two studies, published simultaneously by Nature Genetics and the New England Journal of Medicine, were carried out by two consortiums of scientists, from the US and Cambridge University in Britain.
The genetic variants were unearthed thanks to a comparison of more than 20,000 samples of DNA, provided by patients diagnosed with MS and those without the disease, living in the US and Europe.
"People have been looking for genes involved in MS for 30 years," said David Hafler, a professor of neurology at Harvard Medical School, a lead author on the IL2-R study.