Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: Meta-analysis of nine studies in the CHARGE consortium

Mol Nutr Food Res. 2015 Jul;59(7):1373-83. doi: 10.1002/mnfr.201400734. Epub 2015 Mar 16.


Scope: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid.

Methods and results: We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid.

Conclusion: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes.

Keywords: FADS1; Gene-diet interactions; Meta-analysis; Omega-3 fatty acids.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyltransferases / genetics
  • Acyltransferases / genetics*
  • Adaptor Proteins, Signal Transducing / genetics
  • Carboxy-Lyases / genetics*
  • Diet*
  • Docosahexaenoic Acids / blood
  • Eicosapentaenoic Acid / blood
  • Erythrocyte Membrane / metabolism
  • Fatty Acid Desaturases / genetics*
  • Fatty Acid Elongases
  • Fatty Acids / blood
  • Fatty Acids / pharmacology*
  • Fatty Acids, Omega-3 / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide


  • Adaptor Proteins, Signal Transducing
  • ELOVL2 protein, human
  • Fatty Acids
  • Fatty Acids, Omega-3
  • GCKR protein, human
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acid Desaturases
  • delta-5 fatty acid desaturase
  • Acyltransferases
  • Acetyltransferases
  • Fatty Acid Elongases
  • 2-acylglycerophosphate acyltransferase
  • Carboxy-Lyases
  • PDXDC1 protein, human

Grant support