title: ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation.
abstract: The objective of this study was to determine whether 5-lipoxygenase (ALOX5) gene 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 of fish oil daily, containing 2.0 g of eicosapentaenoic acid [EPA] and 1.0 g of docosahexaenoic acid [DHA]) or placebo oil (5.0 g of corn/soy mixture). A total of 116 subjects (68% female, 20-59 years old) of African American ancestry enrolled, and 98 subjects completed the study. Neither ALOX5 protein nor arachidonic acid-derived LTB4, LTD4, and LTE4 varied by genotype, but 5-hydroxyeicosatetraenoate (5-HETE), 6-trans-LTB4, 5-oxo-ETE, 15-HETE, and 5,15-diHETE levels were higher in subjects homozygous for the ALOX5 promoter allele containing five Sp1 element tandem repeats ("55" genotype) than in subjects with one deletion (d) (three or four repeats) and one common ("d5" genotype) allele or with two deletion ("dd") alleles. 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.
authors.affiliation: Western Human Nutrition Research Center, US Department of Agriculture, Davis, CA 95616, USA. Charles.Stephensen@ars.usda.gov
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stephensen
authors.forename: Patrice
authors.initials: P
authors.lastname: Armstrong
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.forename: Jillian
authors.initials: J
authors.lastname: Legault
authors.forename: Gertrud U
authors.initials: GU
authors.lastname: Schuster
authors.forename: Darshan
authors.initials: D
authors.lastname: Kelley
authors.forename: Susanna
authors.initials: S
authors.lastname: Vikman
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.forename: Rami
authors.initials: R
authors.lastname: Nassir
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
mesh_terms: D000328:Adult; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D015777:Eicosanoids; D005395:Fish Oils; D015289:Leukotrienes; D004281:Docosahexaenoic Acids; C058722:5-hydroxy-6,8,11,14,17-eicosapentaenoic acid; C059164:15-hydroxy-5,8,11,13,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid; D001094:Arachidonate 5-Lipoxygenase