Genetic and Environmental Factors Affecting Hemostasis in Yup'ik People

• Main Author: Au, Nicholas T.
• Other Authors: Rettie, Allan E
• Format: Thesis
• Language: English
• Published: 2014
• Subjects: fish oil; medicinal chemistry; pharmacogenetics; pufa; vitamin K; Yup'ik; Health sciences; Pharmaceutical sciences; Chemistry; Arctic; Greenland; inuits
• Online Access: http://hdl.handle.net/1773/27531

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 ...