Genetic Predictors ofWeight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes

OBJECTIVEdWe tested genetic associations with weight loss and weight regain in the Di-abetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions (lifestyle and metformin) versus placebo. RESEARCHDESIGNANDMETHODSdSixteen 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). RESULTSdIrrespective of treatment, theAla12 allele atPPARG associatedwith short- and long-term weight loss (20.63 and 20.93 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). CONCLUSIONSdGenetic information may help identify people who require additional support to maintain reduced weight after clinical intervention. Diabetes Care 35:363–366, 2012 Multiple obesity-predisposing genevariants are known (1,2), whichmay interact with lifestyle tomod-ify obesity risk (3). It is unknownwhether these variants influence weight regain (WR) after intentional weight loss (WL). We therefore tested associations of 16 obesity-predisposing variants with weight change in Diabetes Prevention Program (DPP) participants