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Multiple sclerosis (MS) affects women more commonly than men. In some regions of the world, there is a relatively rapid increase in the incidence of MS in women.1,2 This observation has 2 possible explanations, resulting either directly from genetic factors or from interaction of the environment with genetic factors. Given the rapidity of increase in the sex ratio there does not seem to be enough evolutionary time to spread a purely genetic risk and therefore the latter seems to be the more likely explanation.
It is well-documented that there is a parent-of-origin effect in MS, i.e., the gender of the parent with MS modifies the risk of their children inheriting MS.3 To date there has been no MS risk gene that has been localized to the X-chromosome or mitochondrial genome that is a sufficiently strong risk factor to explain a parent-of-origin effect in overall inheritance of MS. A rapid rise in the incidence of MS in women would also not allow enough time for such Mendelian mechanisms to develop. However, epigenetic modifications of gene expression (regardless of the chromosome), such as can occur by DNA methylation or histone acetylation, can be induced by environmental exposures and therefore can happen rapidly in an individual's lifetime. These environmentally induced changes can be inherited to the next generation, could be sustained through successive generations if the environmental exposure continues, and importantly could be influenced both by the …
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