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Genetic and epidemiologic aspects of multiple sclerosis in British Columbia Sadovnick, Adele D.

Abstract

The etiology of multiple sclerosis (MS) remains unknown despite much research. The controversy about a genetic component to MS has been going on for nearly a century. Using various sources, the two main ones being the British Columbia (B.C.) Health Surveillance Registry and the B.C. Division of the MS Society of Canada, 983 persons, reported to have MS and living in B.C. on April 30, 1976, were ascertained. These data give a prevalence rate for the province of 39.9 per 100,000 population and a female:male sex ratio of 1.9:1. These findings are what is expected for a northern, temperate region such as B.C. Genetic and medical histories were obtained for 416 of the ascertained patients. Empiric familial recurrence risks, needed for genetic counselling, were derived for first, second, and third degree relatives of patients. The family data were tested for "goodness-of-fit" to the multifactorial two-threshold model of inheritance. This model was rejected on the basis that "too many" families with at least two affected siblings were observed than can be expected under the model. This is evidence for either (a) a genetic model with a higher recurrence risk than the multifactorial model or (b) genetic heterogeneity. There is evidence for phenotypic heterogeneity in MS. Patients with a family history of the disease tend to develop MS at an earlier age than do those with no family history. Pregnancy increases the risk of an exacerbation during a "pregnancy year", particularly during the three months postpartum. However, pregnancy does not appear to affect the long-term prognosis for MS. In summary, the results from this study confirm the findings of others that a genetic factor (or factors) is associated with the manifestation of MS and that there is an increased frequency of the disease among relatives of patients compared with the general population. While the precise genetic model is unclear, recurrence risk estimates have been derived for the first time. Hence genetic counselling is recommended for all MS patients and their families.

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