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Multiple sclerosis in Asian populations : the genetic and environmental determinants of variable susceptibility and clinical profile

University of British Columbia

Multiple sclerosis is a chronic, inflammatory disorder of the central nervous system, thought to primarily affect persons of Caucasian ancestry. Despite growing recognition of multiple sclerosis and clinical variants such as neuromyelitis optica in persons of other ethnicities, relevant research in emerging populations is comparatively scant. Consequently, current understanding with respect to clinical outcomes and risk factors in this ethnic group is remarkably under-developed. The overarching objective of this dissertation was to address these knowledge gaps using a multi-disciplinary approach focusing on Asian-ethnic populations in Canada and China. The prevalence of multiple sclerosis in an Asian-ethnic population of Canada was found to be intermediate to that typically reported in Asia and in the general Canadian population. Longitudinal analysis also revealed an increase in incidence among females of Asian ancestry in Canada. In comparative analysis in a Canadian clinic population, long-term clinical outcomes of multiple sclerosis in patients of Asian ancestry were remarkably similar to those in non-Asian patients. Male sex and later age at onset were associated with less favourable clinical outcomes, irrespective of ethnicity or region. In immigrant and Canadian-born patients, duration of exposure to the Canadian environment prior to onset was associated with multiple sclerosis, whereas exposure to the regional environment of Asia was associated with neuromyelitis optica. Case-control analysis revealed a robust association of smoking with multiple sclerosis risk and clinical outcomes in Canadians of Asian ancestry. Genetic studies confirmed the overall low rate of familial recurrence in this ethnic group, but also identified novel variants associated with risk and clinical phenotypes. The findings underscore the importance of ethnicity-related genetic and environmental factors in modifying susceptibility to and clinical presentation of multiple sclerosis and related disorders in persons of Asian ancestry. Nevertheless, these results also suggest that the clinical trajectory in patients of Asian ancestry may be more comparable to classic clinical descriptions than previously believed. Taken together, the findings presented in this dissertation contribute new perspectives to the epidemiology and etiology of multiple sclerosis and related disorders, and advance knowledge in an emerging patient population in Canada and globally.

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2014-08-11

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/49974

Medical Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/