Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention

SCOPE: People who carry the apolipoprotein E4 (APOE4) SNP have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though inter-individual 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 (PBMC) whole genome gene expression at baseline and following a fish-oil intervention. 

METHODS AND RESULTS: Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and PBMC 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 non-carriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and non-carriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and interferon (IFN) signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only. 

CONCLUSION: 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. This article is protected by copyright. All rights reserved.