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dc.contributor.authorOlsen, Karina Standahl
dc.contributor.authorFenton, Christopher Graham
dc.contributor.authorFrøyland, Livar
dc.contributor.authorWaaseth, Marit
dc.contributor.authorPaulssen, Ruth H
dc.contributor.authorLund, Eiliv
dc.date.accessioned2014-02-12T13:01:56Z
dc.date.available2014-02-12T13:01:56Z
dc.date.issued2013
dc.description.abstractHigh blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a “physiological switch” towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the onset and progression of disease.en
dc.descriptionThis paper is part of Karina Standahl Olsen's doctoral thesis, available in Munin at <a href=http://hdl.handle.net/10037/5442>http://hdl.handle.net/10037/5442</a>en
dc.identifier.citationPLoS ONE (2013), vol. 8(6): e67270en
dc.identifier.cristinIDFRIDAID 1054661
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0067270
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/5825
dc.identifier.urnURN:NBN:no-uit_munin_5520
dc.language.isoengen
dc.publisherPublic Library of Science (PLoS)en
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en
dc.titlePlasma Fatty Acid Ratios Affect Blood Gene Expression Profiles - A Cross-Sectional Study of the Norwegian Women and Cancer Post-Genome Cohorten
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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