Researchers uncover risk factors forMultiple Sclerosis
Research carried out at the Wellcome Trust Centre for Human Genetics has revealed that genetic and environmental factors interact with each other to determine much of the susceptibility to Multiple Sclerosis (MS).
For example, the risk of MS is influenced by parent-of-origin effects. It was observed that there was a higher than average number of mother-daughter pairs with MS and a lower than average number of father-son pairs. Family studies have also revealed that the concordance for MS is far higher between maternally related half siblings than between paternally related ones. It has been shown that MS is virtually absent in the Aboriginal population of Canada. Reasoning that an MS patient who has an Aboriginal and a Caucasian parent, MS is transmitted from the Caucasian parent, researchers compared the risks of MS in offspring who have an Aboriginal mother and a Caucasian father and vice versa. They found a significantly increased risk for MS in the offspring who had a Caucasian mother and an Aboriginal father. This novel method of analysis further implicates maternal effects in MS.
An intriguing relationship also exists between month of birth and the risk of developing MS. A pooled analysis of over 40,000 patients from Canada, Great Britain, Denmark, and Sweden showed that fewer people with MS were born in November and more in May. This observation suggests a role for the intrauterine environment in influencing MS risk but the mechanism of this effect needs to be uncovered. In a study of over 8500 MS patients and controls, researchers were able to show that the main genetic risk factor for MS, a gene on chromosome 6 called HLA-DRB1*15, appears to underlie the month of birth effect in MS with more MS patients carrying this gene who were born in the spring and less people carrying this gene who were born in the winter. This implicates gene-environment interactions. Studies at the WTCHG have previously shown that HLA-DRB1*15 is regulated by vitamin D and, given that vitamin D varies seasonally, it may be that a vitamin D-HLA interaction underlies the month of birth effect in MS but this requires further study.
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Diagram of the structure of the HLA-DRB1 protein, highlighting amino acids thought to be potentially important in influencing MS risk.