title: The effect of the apolipoprotein E genotype on response to personalized dietary advice intervention: findings from the Food4Me randomized controlled trial.
abstract: The apolipoprotein E (APOE) risk allele (ɛ4) is associated with higher total cholesterol (TC), amplified response to saturated fatty acid (SFA) reduction, and increased cardiovascular disease. Although knowledge of gene risk may enhance dietary change, it is unclear whether ɛ4 carriers would benefit from gene-based personalized nutrition (PN).
  
  
  
  The aims of this study were to 1) investigate interactions between APOE genotype and habitual dietary fat intake and modulations of fat intake on metabolic outcomes; 2) determine whether gene-based PN results in greater dietary change than do standard dietary advice (level 0) and nongene-based PN (levels 1-2); and 3) assess the impact of knowledge of APOE risk (risk: E4+, nonrisk: E4-) on dietary change after gene-based PN (level 3).
  
  
  
  Individuals (n = 1466) recruited into the Food4Me pan-European PN dietary intervention study were randomly assigned to 4 treatment arms and genotyped for APOE (rs429358 and rs7412). Diet and dried blood spot TC and ω-3 (n-3) index were determined at baseline and after a 6-mo intervention. Data were analyzed with the use of adjusted general linear models.
  
  
  
  Significantly higher TC concentrations were observed in E4+ participants than in E4- (P < 0.05). Although there were no significant differences in APOE response to gene-based PN (E4+ compared with E4-), both groups had a greater reduction in SFA (percentage of total energy) intake than at level 0 (mean ± SD: E4+, -0.72% ± 0.35% compared with -1.95% ± 0.45%, P = 0.035; E4-, -0.31% ± 0.20% compared with -1.68% ± 0.35%, P = 0.029). Gene-based PN was associated with a smaller reduction in SFA intake than in nongene-based PN (level 2) for E4- participants (-1.68% ± 0.35% compared with -2.56% ± 0.27%, P = 0.025).
  
  
  
  The APOE ɛ4 allele was associated with higher TC. Although gene-based PN targeted to APOE was more effective in reducing SFA intake than standard dietary advice, there was no difference between APOE "risk" and "nonrisk" groups. Furthermore, disclosure of APOE nonrisk may have weakened dietary response to PN. This trial was registered at clinicaltrials.gov as NCT01530139.
authors: Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, United Kingdom.
authors: Rosalind
authors: 0000-0003-3734-6489
authors: R
authors: Fallaize
authors: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: Carlos
authors: 0000-0003-2612-3917
authors: C
authors: Celis-Morales
authors: Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, United Kingdom.
authors: Anna L
authors: 0000-0003-0368-9336
authors: AL
authors: Macready
authors: Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, Netherlands.
authors: Cyril Fm
authors: 0000-0002-4725-6359
authors: CF
authors: Marsaux
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Hannah
authors: 0000-0001-5944-8027
authors: H
authors: Forster
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Clare
authors: C
authors: O'Donovan
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Clara
authors: C
authors: Woolhead
authors: Center for Nutrition Research, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; and Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
authors: Rodrigo
authors: R
authors: San-Cristobal
authors: ZIEL Research Center of Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, Munich, Germany.
authors: Silvia
authors: S
authors: Kolossa
authors: ZIEL Research Center of Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, Munich, Germany.
authors: Jacqueline
authors: J
authors: Hallmann
authors: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
authors: Christina
authors: C
authors: Mavrogianni
authors: National Food and Nutrition Institute (IZZ), Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Surwillo
authors: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: Katherine M
authors: KM
authors: Livingstone
authors: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
authors: George
authors: G
authors: Moschonis
authors: Center for Nutrition Research, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; and Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
authors: Santiago
authors: S
authors: Navas-Carretero
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Marianne C
authors: 0000-0002-6651-2434
authors: MC
authors: Walsh
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Eileen R
authors: 0000-0001-9465-052X
authors: ER
authors: Gibney
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Lorraine
authors: 0000-0002-7711-7499
authors: L
authors: Brennan
authors: Microbiology and Systems Biology Group, TNO, Zeist, Netherlands.
authors: Jildau
authors: J
authors: Bouwman
authors: Eurogenetica Ltd. Burnham-on-Sea, United Kingdom.
authors: Keith
authors: K
authors: Grimaldi
authors: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
authors: Yannis
authors: Y
authors: Manios
authors: National Food and Nutrition Institute (IZZ), Warsaw, Poland.
authors: Iwona
authors: I
authors: Traczyk
authors: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Christian A
authors: CA
authors: Drevon
authors: Center for Nutrition Research, University of Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; and Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
authors: J Alfredo
authors: JA
authors: Martinez
authors: ZIEL Research Center of Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, Munich, Germany.
authors: Hannelore
authors: H
authors: Daniel
authors: Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, Maastricht, Netherlands.
authors: Wim Hm
authors: WH
authors: Saris
authors: UCD Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland.
authors: Michael J
authors: 0000-0001-5250-361X
authors: MJ
authors: Gibney
authors: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: John C
authors: 0000-0003-3406-3002
authors: JC
authors: Mathers
authors: Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, United Kingdom.  j.a.lovegrove@reading.ac.uk
authors: Julie A
authors: 0000-0001-7633-9455
authors: JA
authors: Lovegrove
mesh_terms: D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D018752:Diet, Fat-Restricted; D034742:Electronic Mail; D005060:Europe; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D020407:Internet; D008297:Male; D054647:Nutrigenomics / Q000379:methods; D010349:Patient Compliance; D010352:Patient Dropouts; D010353:Patient Education as Topic; D020641:Polymorphism, Single Nucleotide; D011177:Postal Service; D057285:Precision Medicine
chemical_list: D053327:Apolipoprotein E4; D015525:Fatty Acids, Omega-3; D002784:Cholesterol
keywords: APOE; Food4Me; dietary fat; nutrigenomics; personalized nutrition