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Title: Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans

item ARMSTRONG, PATRICE - University Of California
item Kelley, Darshan
item Newman, John
item STAGGERS, FRANK - Alta Bates Summit Medical Center
item HARTIALA, JAANA - University Of California
item ALLAYEE, HOOMAN - University Of California
item Stephensen, Charles

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2012
Publication Date: 8/1/2012
Citation: Armstrong, P., Kelley, D.S., Newman, J.W., Staggers, F., Hartiala, J., Allayee, H., Stephensen, C.B. 2012. Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans. Journal of Nutrition. 142(8):1417-1428. DOI: 10.3945/jn.112.159814.

Interpretive Summary: Omega-3 fatty acid intake from food or supplements decreases risk of cardiovascular disease (CVD) by several mechanisms, including decreasing plasma triglyceride levels. The 5-lipoxygenase gene (ALOX5) encodes an enzyme that catalyzes the metabolism of some omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) from fish oil. These metabolites may affect the change in plasma triglyceride levels normally seen with increased intake of omega-3 fatty acids. Previous work has shown that variants in this gene may interact with dietary omega-3 intake to affect CVD risk. This may occur because the gene variants may have different capacities to metabolize EPA. The present study was designed to determine if subjects with putative high and low risk variants of the gene had different responses to an intervention with fish oil, a rich source of omega-3 fatty acids. The study randomized volunteers of African ancestry with the putative high and low risk variants of the ALOX5 gene to receive fish oil or placebo oil. Subjects of African ancestry were recruited because they have a higher prevalence of the high risk variant of the ALOX5 gene. The study found that all subjects, regardless of genotype, had similar reductions in plasma triglyceride levels in response to the fish oil supplementation. Thus, if the ALOX5 gene variants do affect risk of CVD the mechanism does not appear to involve changes in the plasma triglyceride response to fish oil supplementation.

Technical Abstract: Objective: To determine the effects of arachidonate 5-lipoxygenase gene (ALOX5) variants on plasma lipid and lipoprotein concentrations and changes in response to fish oil supplementation. We hypothesized that Sp1 variants in the ALOX5 promoter, which have previously been associated with cardiovascular disease (CVD)-related traits, would affect baseline lipid and lipoprotein concentrations and response to dietary intervention. Design: A randomized, double-masked intervention trail that allocated subjects to fish oil (5.0 g fish oil concentrate daily containing 2.0 g eicosapentaenoic acid [EPA] and 1.0 g docosahexaenoic acid [DHA]) or placebo oil (5.0 g of a corn/soy mix) within genotype groups. Of 116 subjects (70% female, 20 - 59 yr) of African ancestry enrolled, 98 completed the study. Results: Fish oil treatment increased erythrocyte EPA mean concentration from 0.43 to 1.72 mol% (p < 0.001) and DHA from 3.46 to 4.62% (p < 0.001). Fish oil treatment also decreased total triglyceride concentration by 20%, with significant decreases in VLDL particle and triglyceride concentrations. Fish oil decreased total cholesterol by 3.0% with significant decreases in intermediate LDL and small HDL cholesterol concentrations. Promoter variants in the ALOX5 gene were not associated with differences in lipid or lipoprotein concentrations at baseline or in response to the fish oil intervention. Conclusions: Fish oil significantly decreased plasma triglyceride and cholesterol concentrations in subjects of African ancestry, as has been demonstrated in other ethnic groups. Gene-dietary associations of ALOX5 promoter variants with risk of CVD phenotypes do not appear to be mediated via effects on lipoprotein metabolism.