APOE genotype modifies the association between plasma omega-3 fatty acids and plasma lipids in the Multi-Ethnic Study of Atherosclerosis (MESA)



      The benefits of fish oil fatty acids eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on plasma lipid profiles have been inconsistent but may partially depend on individual Apolipoprotein E (APOE) genotypes. We aimed to determine whether APOE genotype modifies the association of lipid profile characteristics with plasma EPA and DHA levels.


      APOE genotype was determined in this cross-sectional analysis of 2340 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Relative plasma phospholipid EPA and DHA levels, plasma lipids, and lipoprotein subclass particle sizes and concentrations were measured.


      Significant gene-EPA interactions were found with HDL-C, and particle concentrations of large and total HDL (pinteraction = 0.0002, 0.006, and 0.007, respectively). The above lipid targets were positively associated with EPA in the E2 groups, whereas negative trends were observed among the E4 participants. Gene-DHA interactions were noted for small LDL particle concentrations alone (pinteraction = 0.01), where a positive trend was found among E4 but not E2 or E3 participants.


      These results indicate a significant contribution of the APOE genotype to the EPA-lipid profile relationship; however, the results do not explain the differences in previous findings regarding LDL-C, triglycerides or total cholesterol. Future investigators examining the effects of EPA on HDL-C or lipoprotein characteristics may consider including APOE genotype in their analyses.


      • A cross-sectional study among 2340 free-living and apparently healthy subjects.
      • APOE genotype, plasma phospholipid EPA, DHA, and plasma lipid profiles were measured.
      • APOE-EPA interactions were found with HDL-C, and large and total HDL particles.
      • An APOE-DHA interaction was found for small LDL particle concentrations.


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