title: Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.
abstract: BACKGROUND
  Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis.
  
  
  OBJECTIVE
  We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial.
  
  
  METHODS
  The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured.
  
  
  RESULTS
  By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ.
  
  
  CONCLUSIONS
  Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.
authors: Department of Nutrition, Harvard School of Public Health, Boston, MA (KM, MX, QQ, FS, and LQ); the Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA (LdJ and GAB); and the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (LQ).
authors: Khadijeh
authors: K
authors: Mirzaei
authors: Min
authors: M
authors: Xu
authors: Qibin
authors: Q
authors: Qi
authors: Lilian
authors: L
authors: de Jonge
authors: George A
authors: GA
authors: Bray
authors: Frank
authors: F
authors: Sacks
authors: Lu
authors: L
authors: Qi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001481:Basal Metabolism; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics* / Q000378:metabolism; D004038:Diet, Reducing; D004734:Energy Metabolism; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics; D050177:Overweight / Q000178:diet therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D044122:Receptor, Melatonin, MT1 / Q000235:genetics* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2
chemical_list: D001786:Blood Glucose; C538966:CRY2 protein, human; D056931:Cryptochromes; C573871:MTNR1B protein, human; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2