title: Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain.
abstract: BACKGROUND
  Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI.
  
  
  OBJECTIVE
  The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI).
  
  
  METHODS
  The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis.
  
  
  RESULTS
  HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed.
  
  
  CONCLUSIONS
  TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Karina
authors.initials: K
authors.lastname: Meidtner
authors.forename: Lars
authors.initials: L
authors.lastname: Angquist
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Rikke Dalgaard
authors.initials: RD
authors.lastname: Hansen
authors.forename: Jytte
authors.initials: J
authors.lastname: Halkjær
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Jane Nautrup
authors.initials: JN
authors.lastname: Ostergaard
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Thorkild Ia
authors.initials: TIa
authors.lastname: Sørensen
authors.forename: Ruth Jf
authors.initials: RJ
authors.lastname: Loos
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D015992:Body Mass Index; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology*; D002149:Energy Intake; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D038321:Glycemic Index; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011446:Prospective Studies; D012044:Regression Analysis; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
chemical_list: D004044:Dietary Proteins; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein