New Gene Interaction Appears to be Associated with Increased MS Risk

A person carrying variants of two particular genes could be almost three times more likely to develop multiple sclerosis, according to the latest findings from scientists at Duke Health and the University of Texas Medical Branch at Galveston.


The research used biological samples from the MURDOCK MS Study. The finding, published in the March 23 issue of the journal Cell, could open the way for new tests to identify people who are at greatest risk of MS and autoimmune disorders, as well as the development of novel drugs, the researchers said.

Multiple sclerosis is a major cause of neurological disease in younger adults between the ages of 20 and 50 and disproportionally affects women. The disease causes the body’s own immune system to attack nerve cells in the spinal cord and brain, causing problems with vision, muscle control, balance, and basic body functions. Current MS therapies have adverse side effects, and there is no cure for MS.


“Our study identifies an interaction with a known MS risk gene to unlock a new MS candidate gene, and in doing so, establishing a novel mechanism that is associated with the risk of multiple sclerosis and other autoimmune diseases,” said co-lead author Simon Gregory, Ph.D., principal investigator for the MURDOCK MS Study and director of Genomics and Epigenetics at the Duke Molecular Physiology Institute.


Gregory — along with colleagues at UTMB, the University of California, Berkeley, and Case Western Reserve University — found two particular DNA variants that appear to play a role in MS. One of these variants is in IL7R, a gene previously associated with MS, and the other in DDX39B, a gene not previously connected to the disease.


When the two are present in a person’s genetic code, their interaction can lead to an over-production of a protein called sIL7R. That protein’s interactions with the body’s immune system plays an important, but not completely understood, role in MS.


Researchers used MURDOCK MS Study samples to examine the chromosomal differences between DDX39B and IL7R.


The researchers said this information could potentially be used to craft new tests to diagnose MS, or to improve therapeutic toolkits to fight MS and other autoimmune disorders.


The research was supported by the National Institutes of Health, National MS Society Pilot Award, Duke University Whitehead Scholarship, Ruth and A. Morris Williams Faculty Research Prize funds from Duke University School of Medicine, start-up funds from UTMB, and funds from philanthropist Herman Stone and his family for MS research.

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