Studying human cells isolated in the laboratory, researchers reveal a novel interaction between two genes that influence susceptibility to developing MS, certain environmental factors, and a chemical process (called N-glycosylation) that modifies the structure of molecules, which together may contribute to our understanding of how complex interactions lead to the development of MS. Michael Demetriou, MD, PhD (University of California, Irvine) and colleagues have published these findings in Nature Communications (May 31, 2011, Volume 2, Article #334). The team was funded in part by the National MS Society.This is an area that interests me. MS does not "run" in my family (I am aware of one other person in my family with MS who is a distant relative), but the susceptibility of developing MS being genetic scares me because I would like to have children, but I worry that they could develop MS because they will have a higher probability of developing MS because of their genetic disposition. Scary! I am, however, glad to continue to read that MS is not 100% genetic.
Background: The cause of MS is still not known, but scientists believe that a combination of several factors may be involved to trigger the immune attack that is launched on the brain and spinal cord. While MS is not directly inherited, genes are known to make people susceptible to developing the disease. Researchers also are working to understand how MS gene variations may interact with some environmental triggers that have been linked to MS, such as viral infection, cigarette smoking and low levels of vitamin D/sunlight to increase the risk of MS.
Michael Demetriou, MD, PhD, has previously shown that changes in the addition of specific sugars to proteins involved in the MS attack (N-glycosylation) trigger a spontaneous MS-like disease in mice, which could be suppressed by interfering with the process with a dietary supplement. The current study aimed at translating this finding to the development of human disease.
The Study: In this study, Dr. Demetriou’s team examined DNA samples from about 13,000 people with MS or controls. They looked at how four previously reported susceptibility genes that are involved in immune system activities (interleukin-7 receptor-alpha, interleukin-2 receptor-alpha, MGAT1 and CTLA-4) affect N-glycosylation. Then they examined how a particular environmental factor such as vitamin D affected this interaction.
The results suggest that these genes do alter N-glycosylation in cells isolated in the laboratory, but that both vitamin D and a dietary supplement called N-acetylglucosamine (GlcNAc) were able to suppress this process in cells and in mouse models of MS.
Comment: This study provides new evidence for a link between genes and the environment in the development of MS. However, additional research is needed before it is possible to generalize these findings to all cases of MS, since this study focused on just a few of the many genetic susceptibility factors linked to MS. More research is also needed to determine whether administering vitamin D and G1cNAc will be helpful in MS. A new clinical trial getting underway with support from the National MS Society will test the ability of vitamin D supplements to alter MS disease activity.
Thursday, June 30, 2011
Genetics and MS
From the NMSS website: