A common variation in a specific gene may be the culprit in people susceptible to developing multiple sclerosis, finds a new study.1
Researchers in Sweden found a common risk factor for not only MS, but also ailments like heart disease and rheumatism. This risk factor is a the gene that links autoimmune diseases like MS to cardiovascular diseases, the first time such a gene has been identified, say the scientists.
Experts on all three diseases collaborated to reach the findings. Their study is published in the May 2005 issue of the journal Nature Genetics.
"This gene variant can be one of the single largest genetic causes of complex diseases with inflammatory components," said Fredrik Piehl, MD, PhD, an associate professor in the department of Clinical Neuroscience at the Karolinska Institutet in Stockholm, who headed the study. "The discovery can now lead to more reliable diagnostics and better treatments for a great number of patients."
Culprit—Immune System Gone Awry?
Multiple sclerosis is the most common neurological disorder diagnosed in young adults. Its causes are not yet fully understood, but it is thought to be an autoimmune disease. The disease affects the brain and spinal cord by damaging or destroying a kind of protective insulation that covers nerves known as myelin (MYE-uh-lin). The nerves themselves can also be damaged at the onset of MS. As a result, messages from the central nervous system to the rest of the body may short circuit, causing reduced or lost body functions. Symptoms, however, vary individual-to-individual. These include fatigue, visual disorders, numbness, dizziness, bladder and bowel dysfunction, weakness, tremor, impaired mobility, sexual dysfunction, slurred speech, and spasticity.2
The origins of the disease are believed to lie in an abnormality of the immune system, in which white blood cells—normally charged to fight off infection or disease—are instead guided to target and attack the body's own cells. This causes inflammation in the brain and spinal cord which, in turn, can cause the injury described above.2
Digging for Genetic Clues
For their analysis, Piehl and his colleagues first identified the abnormal gene in an animal model, and then later studied this gene in a number of patient groups to determine if it was linked to any diseases found in humans. Piehl's group learned that those with the gene variant faced up to a 40% greater risk of developing multiple sclerosis, rheumatism, or myocardial infarction—the medical term for heart attack.
They also discovered that the gene variant is relatively common in people, affecting up to 25 percent of the general population.
This discovery, they say, has implications for statins—anti-cholesterol medications that may be effective against multiple sclerosis. The drugs work by easing the inflammatory effects of MS. They do that by reducing the activity of the gene variant discovered in this study, experts contend.3-5
As a result of this knowledge, clinical trials of statins as a therapy for MS have been published in recent years, as well as animal studies of the effectiveness of statins against an MS-like disease.6-8
"There is a chance that other diseases are also affected by this gene variant," Piehl explained.
For instance, the gene variant has shown it can reduce the production of a number of immune defense proteins, and some viruses and bacteria have shown they can influence the gene in an attempt to evade immune system attacks as they mount an infection in the body.9
1. Swanberg M, Lidman O, Padyukov L et al. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis, and myocardial infarction. Nat Genet 2005 May;37(5):486-94. Epub 2005 Apr 10.
2. Multiple Sclerosis Society of America. What is Multiple Sclerosis. Available at: http://www.msaa.com/publications/allaboutms/p_01_whatis.html. Accessed June 3, 2005.
3. Steffens S, Mach F. Anti-inflammatory properties of statins. Semin Vasc Med 2004 Nov;4(4):417-22.
4. Crisby M. Modulation of the inflammatory process by statins. Timely Top Med Cardiovasc Dis 2005 Mar 1;9:E3.
5. Okazaki H, Nagashima T, Minota S. Immunomodulatory activities of statins. [Translated form Japanese]. Nihon Rinsho Meneki Gakkai Kaishi 2004 Dec;27(6):357-60.
6. Vollmer T, Key L, Durkalski V et al. Oral simvastatin in relapsing-remitting multiple sclerosis. Lancet 2004 May 15;363(9421):1607-8.
7. Mach F. Toward a role for statins in immunomodulation. Mol Interv 2002 Dec;2(8):478-80.
8. Youssef S, Stuve O, Patarroyo JC et al. The HMG-CoA reductase inhbitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002 Nov 7;420(6911):78-84.
9. Hiasa Y, Takahashi H, Shimizu M et al. Major histocompatibility complex class-I presentation impaired in transgenic mice expressing hepatitis C virus structural proteins during dendritic cell maturation. J Med Virol 2004 Oct;74(2):253-61.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.