Genetic and Environmental Factors Affecting Hemostasis in Yup'ik People

Thesis (Ph.D.)--University of Washington, 2014 Fish oil has been widely studied for its protective effects against heart disease. These effects are attributed to omega-3 PUFA content, which are also found in sea mammals in addition to fish. The mechanism by which omega-3 PUFAs provide cardiovascular...

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Bibliographic Details
Main Author: Au, Nicholas T.
Other Authors: Rettie, Allan E
Format: Thesis
Language:English
Published: 2014
Subjects:
Online Access:http://hdl.handle.net/1773/27531
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Summary:Thesis (Ph.D.)--University of Washington, 2014 Fish oil has been widely studied for its protective effects against heart disease. These effects are attributed to omega-3 PUFA content, which are also found in sea mammals in addition to fish. The mechanism by which omega-3 PUFAs provide cardiovascular benefits remain unclear but experimental data have alluded to effects on hemostasis. Omega-3 PUFAs may also modify bleeding risk based on anecdotal reports in the literature. The studies presented in this dissertation examine the effect of omega-3 PUFA consumption on measures of hemostasis among Yup'ik study participants, for whom fish and marine mammals are a dietary staple. Measures of clotting potential included clotting factors II and V, PT/INR, PTT, and sP-selectin. These data were assessed for an association with d15N, a validated biomarker of omega-3 PUFA intake. We found that the platelet biomarker, sP-selectin, correlated strongly and inversely with d15N. This supports earlier findings of diminished platelet activation in Greenland Inuits and suggests that platelet activity varies with omega-3 PUFA content in blood. There was also an unexpected bimodal distribution in plasma clotting factor V activity where approximately 11% of samples had values below 30%. While we validated the factor V activity data by measuring factor V protein concentrations by ELISA, the low values were not produced during repeat visits by some of the same individuals. This observation warrants investigation. We then explored whether low vitamin K status is evident in Yup'ik people. Given that the main dietary source of vitamin K is green leafy vegetables, which are only intermittently available in the remote sub-Arctic regions where the Yup'ik live, and that vitamin K is necessary for the production of vitamin K-dependent clotting factors, it is plausible that this population may be more prone to a hypocoagulable state because of limited vitamin K intake. We further hypothesized that Yup'ik people may also harbor unique ...