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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #348550

Research Project: Genomics, Nutrition, and Health

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: 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

item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FOLLIS, JACK - University Of St Thomas
item NETTLETON, JENIFER - University Of Texas
item FOY, MILLENNIA - University Of Texas
item WU, JASON - University Of Sydney
item MA, YIYI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TANAKA, TOSHIKO - National Institute On Aging (NIA, NIH)
item MANICHAKUL, ANI - University Of Virginia
item WU, HONGYU - Harvard Institute
item CHU, AUDREY - Brigham & Women'S Hospital
item STEFFEN, LYN - University Of Minnesota
item FORNAGE, MYRIAM - University Of Texas
item MOZAFFARIAN, DARIUSH - Harvard University
item KABAGAMBE, EDMOND - Vanderbilt University
item FERRUCI, LUIGI - National Institute On Aging (NIA, NIH)
item CHEN, YII-DER IDA - Ucla Medical Center
item RICH, STEPHEN - University Of Virginia
item DJOUSSE, LUC - Brigham & Women'S Hospital
item RIDKER, PAUL - Harvard University
item TANG, WEIHONG - University Of Minnesota
item MCKNIGHT, BARBARA - University Of Washington
item TSAI, MICHAEL - University Of Minnesota
item BANDINELLI, STEFANIA - Azienda Sanitaria Di Firenze
item ROTTER, JEROME - Ucla Medical Center
item HU, FRANK - Harvard University
item CHASMAN, DANIEL - Harvard University
item PSATY, BRUCE - Group Health Cooperative
item ARNETT, DONNA - University Of Alabama
item KING, IRENA - University Of New Mexico
item SUN, QI - Harvard University
item WANG, LU - Brigham & Women'S Hospital
item LUMLEY, THOMAS - University Of Auckland
item CHIUVE, STEPHANIE - Harvard University
item SISCOVICK, DAVID - Group Health Cooperative
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LEMAITRE, ROZENN - Group Health Cooperative

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2015
Publication Date: 7/1/2015
Citation: Smith, C.E., Follis, J.L., Nettleton, J.A., Foy, M., Wu, J.H., Ma, Y., Tanaka, T., Manichakul, A.W., Wu, H., Chu, A.Y., Steffen, L.M., Fornage, M., Mozaffarian, D., Kabagambe, E.K., Ferruci, L., Chen, Y., Rich, S.S., Djousse, L., Ridker, P.M., Tang, W., Mcknight, B., Tsai, M.Y., Bandinelli, S., Rotter, J.I., Hu, F.B., Chasman, D.I., Psaty, B.M., Arnett, D.K., King, I.B., Sun, Q., Wang, L., Lumley, T., Chiuve, S.E., Siscovick, D.S., Ordovas, J.M., Lemaitre, R.N. 2015. 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. Molecular Nutrition and Food Research. 59(7):1373-1383.

Interpretive Summary: Omega-3 fatty acids in the blood appear to be protective against cardiovascular disease, and the evidence is most consistent for the omega-3 fatty acids that are referred to as "long-chain" fatty acids. While blood concentrations are determined in part by dietary intakes of these fatty acids, genetic factors that affect fatty acids' conversion and synthesis also play a role in determining their blood concentrations. Examining the relationships between dietary and genetic factors in combination may be more informative than limiting study to either diet or genetics alone. Previous genetic studies identified a set of genes that are important contributors to omega-3 concentrations. In the current study, we selected a small number of genetic variants from a previous large-scale study, and we explored the impact of diet and genotype using data from nine populations. Of the genetic factors we explored, the variant FADS1 (fatty acid desaturase 1,) which encodes an enzyme in the pathway that converts shorter-chain fatty acids to longer-chain fatty acids, emerged as a potential modulator of omega-3 fatty acids in the blood. Accumulating evidence suggests that carriers of FADS1 variants have reduced capacity to synthesize longer chain omega-3 fatty acids, which may be relevant to dietary recommendations. The long-term objective of gene-diet interaction studies such as this one is to more effectively prevent disease through the development of tailored dietary recommendations that are based on the genetic background of the individual.

Technical Abstract: 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.