title: Homozygous carriers of the TCF7L2 rs7903146 T-allele show altered postprandial response in triglycerides and triglyceride-rich lipoproteins.
abstract: The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers. All participants consumed a test meal after 12 hours of fasting. Metabolites were measured using proton nuclear magnetic resonance (NMR) spectroscopy. Metabolomic profiling of TCF7L2 carriers were performed for 141 lipid estimates. TT carriers had lower fasting levels of L-VLDL-L (total lipids in large very low density lipoproteins, p = 0.045), L-VLDL-CE (cholesterol esters in large VLDL, p = 0.03), and L-VLDL-C (total cholesterol in large VLDL, p = 0.045) compared to CC carriers. Additionally, TT carriers had lower postprandial levels of total triglycerides (TG) (q = 0.03), VLDL-TG (q = 0.05, including medium, small and extra small, q = 0.048, q = 0.0009, q = 0.04, respectively), HDL-TG (triglycerides in high density lipoproteins q = 0.037) and S-HDL-TG (q = 0.00003). In conclusion, TT carriers show altered postprandial triglyceride response, mainly influencing VLDL and HDL subclasses suggesting a genotype-mediated effect on hepatic lipid regulation.
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Engelbrechtsen
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: T H
authors.initials: TH
authors.lastname: Hansen
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: Y
authors.initials: Y
authors.lastname: Mahendran
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: P
authors.initials: P
authors.lastname: Pyl
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: E
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: A
authors.initials: A
authors.lastname: Jonsson
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: A
authors.initials: A
authors.lastname: Gjesing
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Denmark.|Department of Clinical Experimental Research, Rigshospitalet, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Research Centre for Prevention and Health, The Capital Region of Denmark, Denmark.|Department of Public health, Faculty of Health Science, University of Copenhagen, Denmark.|Faculty of Medicine, Aalborg University, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Section of Metabolic Genetics, Novo Nordisk Research Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Universitetsparken 1, DIKU-building 1. Floor, DK-2100 Copenhagen.|Steno Diabetes Center, Gentofte, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Vestergaard
mesh_terms: D005838:Genotype; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D019518:Postprandial Period; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
chemical_list: D008074:Lipoproteins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D014280:Triglycerides