F5 Q506 Mutation and the Low Prevalence of Cardiovascular Disease in Canadian Inuit

Background The Keewatin Inuit have a very low age-adjusted mortality rate from vascular diseases compared to the general population of Canada. Interethnic differences in both genetic and lifestyle factors have been offered as explanations for this observation. We previously found that compared to white subjects, the Inuit had a significantly increased prevalence of 4 candidate alleles for atherosclerosis-related phenotypes, namely AGT T235, FABP2 T54, PON1 R192, and APOE E4, and a significantly decreased prevalence of 2 candidate alleles for atherosclerosis-related phenotypes, namely ACE D and MTHFR 677T. Methods We tested the hypothesis that 165 Canadian Inuit would have a significantly different frequency of the thrombosis-associated F5 Q506 allele compared with reference controls. Results We found a complete absence of F5 Q506 in 165 Inuit, which was significantly different from the frequency of 3.92% observed in regional control White subjects. Conclusions The aggregate of results from our studies in Inuit to date suggests that the beneficial influence of the low prevalence of any or all of the ACE D, MTHFR 677T and F5 Q506 outweighs the deleterious influence of the high prevalence of any or all of the other disease-associated alleles. However, it remains possible that other genetic and/or environmental factors determine the low susceptibility to vascular disease in the Inuit.