Multiple sclerosis: Its causes and genetics

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Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. While the cause is unclear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin-producing cells.

CAUSES: The cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as infectious agents. Theories try to combine the data into likely explanations, but none has proved definitive. While there are a number of environmental risk factors and although some are partly modifiable, further research is needed to determine whether their elimination can prevent MS.

GENETICS: MS is not considered a hereditary disease; however, a number of genetic variations have been shown to increase the risk. Some of these genes appear to have higher levels of expression in microglia cells than expected by chance. The probability of developing the disease is higher in relatives of an affected person, with a greater risk among those more closely related.  In identical twins both are affected about 30% of the time, while around 5% for non-identical twins and 2.5% of siblings are affected with a lower percentage of half-siblings. If both parents are affected the risk in their children is 10 times that of the general population.

INFECTIOUS AGENTS: Many microbes have been proposed as triggers of MS, but have been confirmed. Moving at an early age from one location in the world to another alters a person &  subsequent risk of MS. An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare one, is related to the disease. Proposed mechanisms include the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to certain infectious agents early in life is protective; the disease is a response to a late encounter with such agents. The prevalence hypothesis proposes that the disease is due to an infectious agent more common in regions where MS is common and where, in most individuals, it causes an ongoing infection without symptoms. Only in a few cases and after many years does it cause demyelization. The hygiene hypothesis has received more support than the prevalence hypothesis.