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ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation.

Stephensen CB, Armstrong P, Newman JW, Pedersen TL, Legault J, Schuster GU, Kelley D, Vikman S, Hartiala J, Nassir R, Seldin MF, Allayee H

USDA Western Human Nutrition Research Center, United States;

The objective was to determine if 5-lipoxygenase gene (ALOX5) variants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g fish oil 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). 116 subjects (68% female, 20 - 59 yr) of African American ancestry enrolled and 98 completed the study. Neither ALOX5 protein nor arachidonic acid (AA)-derived LTB4, LTD4 and LTE4 varied by genotype but 5-hydroxy eicosatetraenoate (5-HETE), 6 trans-LTB4, 5-oxo-ETE, 15-HETE and 5,15-DiHETE were higher in subjects homozygous for the ALOX5 promoter allele containing 5 Sp1-element tandem repeats (55 genotype) than in subjects with one deletion (3 or 4 repeats) and one common allele (d5) or with two deletion alleles (dd). The EPA-derived metabolites 5-HEPE and 15-HEPE and the DHA-derived metabolite 17-HDoHE had similar associations with genotype and increased with supplementation; 5-HEPE and 15-HEPE increased and 5-oxo-ETE decreased to a greater degree in the 55 than in the other genotypes. This differential eicosanoid response is consistent with the previously observed interaction of these variants with dietary intake of omega-3 fatty acids in predicting cardiovascular disease risk.

Published 7 February 2011 in J Lipid Res.
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