title: Macronutrient Intake-Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial.
abstract: Fibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.
  
  
  
  We genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.
  
  
  
  We observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.
  
  
  
  Our data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake-decreasing allele of the FGF21 variant to improve body composition and abdominal obesity.
authors: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
authors: Yoriko
authors: 0000-0002-0957-9309
authors: Y
authors: Heianza
authors: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors: Wenjie
authors: W
authors: Ma
authors: Epidemiology Domain, Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Tao
authors: T
authors: Huang
authors: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
authors: Tiange
authors: T
authors: Wang
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors: Yan
authors: Y
authors: Zheng
authors: Florida Hospital and Sanford-Burnham Institute, Orlando, FL.
authors: Steven R
authors: SR
authors: Smith
authors: Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.
authors: George A
authors: GA
authors: Bray
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors: Frank M
authors: FM
authors: Sacks
authors: Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA lqi1@tulane.edu.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors: Lu
authors: L
authors: Qi
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001823:Body Composition / Q000235:genetics*; D031204:Caloric Restriction; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004038:Diet, Reducing; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D002149:Energy Intake; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy*; D056128:Obesity, Abdominal / Q000235:genetics; D050177:Overweight / Q000178:diet therapy; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055105:Waist Circumference; D015431:Weight Loss / Q000235:genetics*
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors