title: Vitamin D metabolism-related genetic variants, dietary protein intake and improvement of insulin resistance in a 2 year weight-loss trial: POUNDS Lost.
abstract: OBJECTIVE
  Vitamin D and related genetic variants are associated with obesity and insulin resistance. We aimed to examine whether vitamin D metabolism-related variants affect changes in body weight and insulin resistance in response to weight-loss diets varying in macronutrient content.
  
  
  METHODS
  Three vitamin D metabolism-related variants, DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs2282679, were genotyped in 732 overweight/obese participants from a 2 year weight-loss trial (POUNDS Lost). We assessed genotype effects on changes in body weight, fasting levels of glucose and insulin, and HOMA-IR at 6 months (up to 656 participants) and 2 years (up to 596 participants) in response to low-protein vs high-protein diets, and low-fat vs high-fat diets.
  
  
  RESULTS
  We found significant interactions between DHCR7 rs12785878 and diets varying in protein, but not in fat, on changes in insulin and HOMA-IR at both 6 months (p for interaction <0.001) and 2 years (p for interaction ≤ 0.03). The T allele (vitamin-D-increasing allele) of DHCR7 rs12785878 was associated with greater decreases in insulin and HOMA-IR (p < 0.002) in response to high-protein diets, while there was no significant genotype effect on changes in these traits in the low-protein diet group. Generalised estimating equation analyses indicated significant genotype effects on trajectory of changes in insulin resistance over the 2 year intervention in response to high-protein diets (p < 0.001). We did not observe significant interaction between the other two variants and dietary protein or fat on changes in these traits.
  
  
  CONCLUSIONS
  Our data suggest that individuals carrying the T allele of DHCR7 rs12785878 might benefit more in improvement of insulin resistance than noncarriers by consuming high-protein weight-loss diets.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00072995.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: LSU, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rood
authors.affiliation: LSU, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. lqi1@tulane.edu.|Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA. lqi1@tulane.edu.|Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. lqi1@tulane.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D018753:Diet, Protein-Restricted; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics; D050177:Overweight / Q000178:diet therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014807:Vitamin D / Q000378:metabolism*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D004044:Dietary Proteins; D007328:Insulin; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
keywords: Diet intervention; Genetic variants; Insulin resistance; Vitamin D; Weight loss