An analysis of human genetic variation and vitamin D3, published in Nature Communications, shows that both genes and the environment may interact to cause multiple sclerosis (MS.)
Michael Demetriou and colleagues study the process of N-glycosylation in which certain defects are known to lead to neurodegeneration in mice. They show that genes that are known to be risk factors for MS in humans can affect N-glycan branching in cells in culture, potentially providing a link between the MS risk genes and branching and neurodegeneration The authors demonstrate, using MS case-control cohorts, that variations in known MS risk genes could interact with genetic variants in branching genes to increase odds of developing the disease.
The team go on to examine the role of vitamin D3, which is generated by exposure to sunlight and is also known to be associated with MS and show that it too can promote N-glycan branching in culture and that reducing vitamin D3 levels in mice can block branching in T cells. Taken together the findings suggest a mechanism whereby environment and genetic factors may interact to cause multiple sclerosis.