title: Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.
abstract: OBJECTIVE
  We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo.
  
  
  METHODS
  Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end).
  
  
  RESULTS
  Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (-0.63 and -0.93 kg/allele, P ≤ 0.005, respectively). Gene-treatment interactions were observed for short-term (LYPLAL1 rs2605100, P(lifestyle*SNP) = 0.032; GNPDA2 rs10938397, P(lifestyle*SNP) = 0.016; MTCH2 rs10838738, P(lifestyle*SNP) = 0.022) and long-term (NEGR1 rs2815752, P(metformin*SNP) = 0.028; FTO rs9939609, P(lifestyle*SNP) = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P(lifestyle*SNP) < 0.05).
  
  
  CONCLUSIONS
  Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.
authors.affiliation: Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Delahanty
authors.forename: Qing
authors.initials: Q
authors.lastname: Pan
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: Karol E
authors.initials: KE
authors.lastname: Watson
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Alan
authors.initials: A
authors.lastname: Shuldiner
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001835:Body Weight / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics* / Q000517:prevention & control*; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008019:Life Style; D008245:Lysophospholipase / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008687:Metformin / Q000627:therapeutic use*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D015430:Weight Gain / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C502207:MTCH2 protein, human; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; C485559:NEGR1 protein, human; D047495:PPAR gamma; D011506:Proteins; C530715:TMEM18 protein, human; D008687:Metformin; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D008245:Lysophospholipase; C561408:LYPLAL1 protein, human