Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program
- Linda M. Delahanty, MS, RD1,2,
- Qing Pan, PHD3,
- Kathleen A. Jablonski, PHD3,
- Karol E. Watson, MD, PHD4,
- Jeanne M. McCaffery, PHD5,
- Alan Shuldiner, MD6,
- Steven E. Kahn, MB, CHB7,
- William C. Knowler, MD, DRPH8,
- Jose C. Florez, MD, PHD1,2,9,10,
- Paul W. Franks, PHD, MPHIL, MS11,12 and
- for the Diabetes Prevention Program Research Group*⇓
- 1Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts
- 2Department of Medicine, Harvard Medical School, Boston, Massachusetts
- 3The Biostatistics Center, George Washington University, Rockville, Maryland
- 4The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
- 5Weight Control and Diabetes Research Center, The Miriam Hospital and Brown Medical School, Providence, Rhode Island
- 6Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, and Program in Genetics and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland
- 7Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington
- 8National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
- 9Center for Human Genetic Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- 10Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts
- 11Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden
- 12Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- Corresponding author: Diabetes Prevention Program Research Group, .
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, Plifestyle*SNP = 0.032; GNPDA2 rs10938397, Plifestyle*SNP = 0.016; MTCH2 rs10838738, Plifestyle*SNP = 0.022) and long-term (NEGR1 rs2815752, Pmetformin*SNP = 0.028; FTO rs9939609, Plifestyle*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 (Plifestyle*SNP < 0.05).
CONCLUSIONS Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.
- Received July 25, 2011.
- Accepted October 23, 2011.
- © 2012 by the American Diabetes Association.
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