Sarah Orton
Post-Doctoral Researcher
Research
My main research interests are environmental factors in MS susceptibility and outcome. This includes primarily epidemiological, observational, and genetic studies. I am particularly interested in gender issues and vitamin D effects.
Over the past several years, we established a significant role for environmental factors in mediating susceptibility to multiple sclerosis. This included demonstration of a true increase in MS incidence over the past century, showing a significant increase in the sex ratio of MS in Canada. The evidence does not target specific environmental mediators of the effect, but there is interesting year to year variation. We also examined sex ratio of immigrants to Canada, showing similar increases, albeit at variable rates. Age at immigration and country of origin were shown to be significant factors in predicting sex ratio changes.
We examined UV exposure and vitamin D as a potential candidate to explain, or in part explain, these observed effects. We showed a significant relationship of UVB and MS prevalence in an ideal homogenous population and the association was stronger in females (data unpublished). We established evidence for genetic regulation of serum vitamin D levels, which could reflect a potential genetic basis of vitamin D effects on MS susceptibility. Findings suggested that one variant in the vitamin D receptor and two variants in the alpha-hydroxylase gene may be influencing patient levels and possibly MS risk. We next studied these variants in a replication cohort of sibling pairs and extremes of outcome cohort.
When serum 25(OH)D levels were measured in MS patients and their families, a high prevalence of vitamin D deficiency amongst MS patients was noted. There was also a clear and reproducible seasonal variation of vitamin D levels. Further studies are underway to determine the relationship between genes and 25(OH)D levels and the relationship to MS susceptibility.
Publications
Orton SM, Herrera BM, Yee IM, Ramagopalan, S. V., Lincoln, M. R.,Chao, M. J.,Vieth, R.,Sadovnick, A. D. and Ebers, G. C. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006;5:932-6.
Orton SM, Morris AP, Herrera BM, et al. Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 2008;88:441-7.
Orton SM, Ramagopalan SV, Brocklebank D, Herrrera BM, Yee IM, Sadovnick AD, and Ebers GE. Effect of immigration on multiple sclerosis gender ratio in Canada: the Canadian Collaborative Study. JNNP, 2008