Genetic prediction of atherosclerosis: lessons from studies in native Canadian populations.

The Oji-Cree from Northern Ontario have a very high prevalence of cardiovascular disease and diabetes mellitus, whereas the Inuit from Nunavut have a very low prevalence of these diseases. There are significant differences between Oji-Cree, Inuit and white subjects with respect to the frequencies of putative 'deleterious alleles' of several candidate genes in diabetes and atherosclerosis. Specifically, compared to whites, both Oji-Cree and Inuit have an excess of 'deleterious alleles' from 12 candidate genes in atherosclerosis and/or diabetes. However, it would appear that these differences in genetic architecture are not sufficient to account for the wide disparity in disease prevalence between the two aboriginal groups. It is very likely that environmental lifestyle factors, such as maintenance of a traditional diet and an increased level of activity, can override an apparent background of genetic susceptibility to these diseases in native people. Full understanding of the genetic component will require more effort because of confounding factors such as small genetic effects, non-mendelian inheritance, gene-gene interactions and gene-environment interactions. However, even before there is a full understanding of the identity of the all the genes involved, and of how their products might contribute to disease susceptibility in an individual or a community, there would be some justification to recommend an intervention strategy at this point in time. Such an intervention strategy would stress a return to a more traditional diet and lifestyle in order to avert and reverse these disease phenotypes in Canadian aboriginal communities.