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.

Pubmed ID: 25626431

Pubmed Central ID: PMC4491005

Journal: Molecular nutrition & food research

Publication Date: July 1, 2015

Affiliation: Cardiovascular Health Research Unit, Department of Medicine, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.

MeSH Terms: Humans, Male, Female, Middle Aged, Polymorphism, Single Nucleotide, Diet, Acyltransferases, Acetyltransferases, Adaptor Proteins, Signal Transducing, Carboxy-Lyases, Docosahexaenoic Acids, Eicosapentaenoic Acid, Erythrocyte Membrane, Fatty Acid Desaturases, Fatty Acids, Fatty Acids, Omega-3, Fatty Acid Elongases, Delta-5 Fatty Acid Desaturase

Grants: HL080295, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169, HHSN268200800007C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 AG023629, R01 HL080295, U01 HL080295, UL1 TR000170, R56 AG023629, N01-HC-95166, N01-HC-95167, N01-HC-95168, UL1 TR000124, UL1TR000124, AG023629, U01 HG004402, R01 HL059367, UL1 RR024156, UL1RR025005, R01HL59367, UL1 RR025005, R01 HL086694, U01HG004402, R01HL087641, R01 HL087641, R01HL086694, P30 DK063491, R01 HL087652, R01 HL105756, HL105756, HL087652, UM1 CA182913, DK063491, K08 HL112845, HL099355, R00-HL095649, U01-HG-004446, U01 HG004446, U01HL072524, R01 HL085710, P01 CA087969, HHSN268201300029C, R01 HL091357, R00HL098459, HHSN268201300025C, R01 MD009164, RR-024156, P01 CA055075, R00 HL098459, HL60712, HL085710, R01 HL35464, R00 HL095649, R01 HL078885, U01 HG004424, R01-HL-084099, HL54776, CA047988, U01 HG004729, HHSN268201300028C, U01 HL072524, HL078885, U01-HG-004424, P01 CA87969, HHSN268201300026C, R01 HL034594, R01 HL084099, HHSN268200900041C, R01 CA047988, U01-HG-004729, R01 HL080467, UM1 CA167552, HL080467, R01 HL035464, HHSN268201300027C, CA055075, R01 HL060712, RC1 HL099355, R01 HL054776, R00 HL097068, N01HC95159, N01HC95169, HHSN268201100009I, HHSN268201100005G, HHSN268201100008I, HHSN268201100011I, HHSN268201100005I, HHSN268201100007I, R01 HL043851, N02HL64278

Authors: Hu FB, Siscovick DS, Wang L, Psaty BM, Wu H, Tanaka T, Bandinelli S, Ridker PM, Rich SS, Tang W, Rotter JI, Lumley T, Fornage M, Chasman DI, Follis JL, Nettleton JA, Lemaitre RN, Mozaffarian D, Smith CE, Djoussé L, Arnett DK, Foy M, Wu JH, Ma Y, Manichakul AW, Chu AY, Steffen LM, Kabagambe EK, Ferruci L, Chen YD, McKnight B, Tsai MY, King IB, Sun Q, Chiuve SE, Ordovás JM

Cite As: Smith CE, Follis JL, Nettleton JA, Foy M, Wu JH, Ma Y, Tanaka T, Manichakul AW, Wu H, Chu AY, Steffen LM, Fornage M, Mozaffarian D, Kabagambe EK, Ferruci L, Chen YD, Rich SS, Djoussé L, Ridker PM, Tang W, McKnight B, Tsai MY, Bandinelli S, Rotter JI, Hu FB, Chasman DI, Psaty BM, Arnett DK, King IB, Sun Q, Wang L, Lumley T, Chiuve SE, Siscovick DS, Ordovás JM, Lemaitre RN. 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. Epub 2015 Mar 16.

Studies:

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.