ALOX5 gene variants affect eicosanoid production and response to fi sh oil supplementation

Charles B. Stephensen, Patrice Armstrong, John W. Newman, Theresa L. Pedersen, Jillian Legault, Gertrud U. Schuster, Darshan Kelley, Susanna Vikman, Jaana Hartiala, Rami Nassir, Michael F Seldin, Hooman Allayee

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17 Scopus citations

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 fi sh oil (5.0 g of fi sh 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 fi ve 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.

Original languageEnglish (US)
Pages (from-to)991-1003
Number of pages13
JournalJournal of Lipid Research
Volume52
Issue number5
DOIs
StatePublished - May 2011

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Keywords

  • Arachidonic acid
  • Eicosanoids
  • Leukotrienes
  • Lipoxygenase
  • Nutrition
  • Omega-3 fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Stephensen, C. B., Armstrong, P., Newman, J. W., Pedersen, T. L., Legault, J., Schuster, G. U., Kelley, D., Vikman, S., Hartiala, J., Nassir, R., Seldin, M. F., & Allayee, H. (2011). ALOX5 gene variants affect eicosanoid production and response to fi sh oil supplementation. Journal of Lipid Research, 52(5), 991-1003. https://doi.org/10.1194/jlr.P012864