title: Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention.
abstract: People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish-oil intervention.
  
  
  
  Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only.
  
  
  
  The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish-oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN-related genes.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.|TNO, Department of Microbiology and Systems Biology, The Hague, The Netherlands.
authors.forename: Juri C
authors.initials: JC
authors.lastname: Matualatupauw
authors.affiliation: TNO, Department of Microbiology and Systems Biology, The Hague, The Netherlands.
authors.forename: Marijana
authors.initials: M
authors.lastname: Radonjic
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Ondine
authors.initials: O
authors.lastname: van de Rest
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Geleijnse
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Afman
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015398:Signal Transduction
chemical_list: D053327:Apolipoprotein E4; D005395:Fish Oils; C573415:IFNG protein, human; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma; D002784:Cholesterol; D015118:Eicosapentaenoic Acid
keywords: APOE4; Fish-oil supplementation; Gene-diet interactions; Microarray; Nutrigenomics