title: Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
abstract: BACKGROUND
  Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial.
  
  
  RESULTS
  We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ≤0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the high-fat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ≤ 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group (P=0.02 and P=0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss (P=0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain.
  
  
  CONCLUSIONS
  Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.
authors: Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.
authors: Min
authors: M
authors: Xu
authors: Qibin
authors: Q
authors: Qi
authors: Jun
authors: J
authors: Liang
authors: George A
authors: GA
authors: Bray
authors: Frank B
authors: FB
authors: Hu
authors: Frank M
authors: FM
authors: Sacks
authors: Lu
authors: L
authors: Qi
mesh_terms: D000328:Adult; D000483:Alleles; D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001835:Body Weight / Q000235:genetics*; D004038:Diet, Reducing; D005260:Female; D033141:Genetic Determinism; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy* / Q000517:prevention & control; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D000071636:Protein Phosphatase 2C; D016896:Treatment Outcome
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D007328:Insulin; C000607462:PPM1K protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C