Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program

Diabetes Care. 2012 Feb;35(2):363-6. doi: 10.2337/dc11-1328. Epub 2011 Dec 16.

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.

Research design and 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.

Trial registration: ClinicalTrials.gov NCT00004992.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Weight / genetics
  • Brain-Derived Neurotrophic Factor / genetics
  • Cell Adhesion Molecules, Neuronal / genetics
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / prevention & control*
  • GPI-Linked Proteins / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Life Style*
  • Lysophospholipase / genetics
  • Membrane Proteins / genetics
  • Metformin / therapeutic use*
  • Mitochondrial Membrane Transport Proteins / genetics
  • PPAR gamma / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Proteins / genetics
  • Weight Gain / genetics*
  • Weight Loss / genetics*

Substances

  • Brain-Derived Neurotrophic Factor
  • Cell Adhesion Molecules, Neuronal
  • GPI-Linked Proteins
  • MTCH2 protein, human
  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • NEGR1 protein, human
  • PPAR gamma
  • Proteins
  • TMEM18 protein, human
  • Metformin
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Lysophospholipase
  • LYPLAL1 protein, human

Associated data

  • ClinicalTrials.gov/NCT00004992