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

Caren E Smith; Jack L Follis; Jennifer A Nettleton; Millennia Foy; Jason H Y Wu; Yiyi Ma; Toshiko Tanaka; Ani W Manichakul; Hongyu Wu; Audrey Y Chu; Lyn M Steffen; Myriam Fornage; Dariush Mozaffarian; Edmond K Kabagambe; Luigi Ferruci; Yii-Der Ida Chen; Stephen S Rich; Luc Djoussé; Paul M Ridker; Weihong Tang; Barbara McKnight; Michael Y Tsai; Stefania Bandinelli; Jerome I Rotter; Frank B Hu; Daniel I Chasman; Bruce M Psaty; Donna K Arnett; Irena B King; Qi Sun; Lu Wang; Thomas Lumley; Stephanie E Chiuve; David S Siscovick; José M Ordovás; Rozenn N Lemaitre

doi:10.1002/mnfr.201400734

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.

Authors

Caren E Smith¹, Jack L Follis², Jennifer A Nettleton³, Millennia Foy⁴, Jason H Y Wu⁵, Yiyi Ma¹, Toshiko Tanaka⁶, Ani W Manichakul^{7

8}, Hongyu Wu⁹, Audrey Y Chu¹⁰, Lyn M Steffen¹¹, Myriam Fornage^{3

4}, Dariush Mozaffarian^{12

13

14}, Edmond K Kabagambe¹⁵, Luigi Ferruci⁶, Yii-Der Ida Chen¹⁶, Stephen S Rich⁸, Luc Djoussé^{17

18}, Paul M Ridker^{10

19}, Weihong Tang¹¹, Barbara McKnight²⁰, Michael Y Tsai²¹, Stefania Bandinelli²², Jerome I Rotter¹⁶, Frank B Hu^{9

23

24

25}, Daniel I Chasman^{10

19}, Bruce M Psaty^{26

27

28}, Donna K Arnett²⁹, Irena B King³⁰, Qi Sun^{9

24

25}, Lu Wang¹⁰, Thomas Lumley³¹, Stephanie E Chiuve⁹, David S Siscovick^{26

27}, José M Ordovás^{1

32

33}, Rozenn N Lemaitre²⁶

Affiliations

¹ Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA*
² Department of Mathematics, Computer Science, and Cooperative Engineering, University of St. Thomas, Houston, TX, USA.
³ Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁵ The George Institute for Global Health, The University of Sydney, Sydney, NSW, Australia.
⁶ Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
⁷ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁸ Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
⁹ Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
¹⁰ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹¹ Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
¹² Department of Epidemiology, Harvard School of Public Health, Harvard Medical School, Boston, MA, USA.
¹³ Department of Nutrition, Harvard School of Public Health, Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁵ Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
¹⁶ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA.
¹⁷ Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁸ Boston Veterans Affairs Healthcare System, Boston, MA, USA.
¹⁹ Harvard Medical School, Boston, MA, USA.
²⁰ Department of Biostatistics, University of Washington, Seattle, WA, USA.
²¹ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
²² Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy.
²³ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
²⁴ Harvard School of Public Health, Boston, MA, USA.
²⁵ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁶ Cardiovascular Health Research Unit, Department of Medicine, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
²⁷ Department of Epidemiology, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
²⁸ Department of Health Services, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
²⁹ Department of Epidemiology, Section on Statistical Genetics, and The Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁰ Department of Internal Medicine, Division of Endocrinology, University of New Mexico, Albuquerque, NM, USA.
³¹ Department of Statistics, University of Auckland, Auckland, New Zealand.
³² Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), Madrid, Spain.
³³ Instituto Madrilenõs de Estudios Avanzados Alimentación, Madrid, Spain.

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.

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*
Delta-5 Fatty Acid Desaturase
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

Substances

Adaptor Proteins, Signal Transducing
Delta-5 Fatty Acid Desaturase
ELOVL2 protein, human
Fatty Acids
Fatty Acids, Omega-3
GCKR protein, human
Docosahexaenoic Acids
Eicosapentaenoic Acid
Fatty Acid Desaturases
FADS1 protein, human
Acyltransferases
Acetyltransferases
Fatty Acid Elongases
2-acylglycerophosphate acyltransferase
Carboxy-Lyases
PDXDC1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding