British Journal of Nutrition

Full Papers

Molecular Nutrition

Influence of SNPs in nutrient-sensitive candidate genes and gene–diet interactions on blood lipids: the DiOGenes study

Lena K. Brahea1 c1, Lars Ängquista2, Lesli H. Larsena1, Karani S. Vimaleswarana3a4, Jörg Hagera5, Nathalie Vigueriea6, Ruth J. F. Loosa3a7, Teodora Handjieva-Darlenskaa8, Susan A. Jebba9, Petr Hlavatya10, Thomas M. Larsena1, J. Alfredo Martineza11, Angeliki Papadakia12, Andreas F. H. Pfeiffera13a14, Marleen A. van Baaka15, Thorkild I. A. Sørensena2a16, Claus Holsta2, Dominique Langina6, Arne Astrupa1 and Wim H. M. Sarisa15

a1 Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark

a2 Institute of Preventive Medicine, Copenhagen University Hospitals, Copenhagen, Denmark

a3 MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

a4 MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, London, UK

a5 CEA Genomics Institute – Centre National de Génotypage, Evry, France

a6 Inserm U1048, Obesity Research Laboratory, Metabolic and Cardiovascular Medicine Institute, University of Toulouse, Toulouse, France

a7 Mount Sinai School of Medicine, New York, NY 10029, USA

a8 National Transport Hospital, Department of Nutrition, Dietetics and Metabolic Diseases, Sofia, Bulgaria

a9 MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK

a10 The Obesity Management Center, Institute of Endocrinology, Prague, Czech Republic

a11 Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain

a12 Department of Social Medicine, University of Crete, Heraklion, Greece

a13 Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany

a14 Department of Endocrinology, Diabetes and Nutrition, Charité Medical University, Berlin, Germany

a15 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands

a16 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark


Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14, P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.

(Received July 06 2012)

(Revised December 12 2012)

(Accepted December 12 2012)

(Online publication January 29 2013)

Key Words:

  • Blood lipids;
  • Gene–diet interactions;
  • Protein;
  • Glycaemic index;
  • SNPs


c1 Corresponding author: L. K. Brahe, fax +45 353 32 483, email


  Abbreviations: DiOGenes, Diet Obesity and Genes; GI, glycaemic index; GWAS, genome-wide association studies; HDL-C, HDL-cholesterol; HGI, high glycaemic index; HP, high dietary protein; LD, linkage disequilibrium; LDL-C, LDL-cholesterol; LED, low-energy diet; LGI, low glycaemic index; LP, low dietary protein; LPIN1, lipin 1; LPL, lipoprotein lipase; MAF, minor allele frequency; MLXIPL, MLX interacting protein-like; PPARGC1A, PPARγ co-activator 1-α; TC, total cholesterol