Abstract P235: Genetic Variants in <i>TCF7L2</i> Modulate Dietary Fat Intake on Changes in Body Composition During a Weight-Loss Intervention

Introduction: Polymorphisms mapping to TCF7L2 have been associated with increased risk of type 2 diabetes, impaired glucose and insulin metabolism, and adiposity. Recent observational studies and short-term randomized trials suggest dietary factors, especially fat, may modify TCF7L2 genotype in relation to weight loss. The effect has yet to be verified in long-term intervention settings. Hypothesis: We assessed the hypothesis that two well-recognized TCF7L2 single nucleotide polymorphisms (SNPs) modulate the response to diets of different fat content, in relation to long-term changes in anthropometry and body composition in a 2 year weight-loss intervention trial. Methods: The effect of TCF7L2 SNPs rs7903146 and rs12255372 on changes at 6 months and 2 years in body mass and body composition measures obtained from DEXA scans was evaluated in 590 overweight/obese Caucasian participants of Pounds Lost, a 2-year weight-loss randomized clinical trial of diets differing in macronutrient proportions. Adjusted means were obtained for variant main effect and for interaction with assigned diet group as low-fat (20% from calories) vs. high-fat diet (40%). Results: After adjusting for age, sex, center, and baseline measure, rs12255372 TT (risk allele) carriers had significantly greater decrease at 6 months in BMI, total body fat and trunk fat mass, and marginal decrease in weight ( P for interaction= 0.042, 0.029, 0.033 and 0.056, respectively), than those without this genotype, when following a low-fat diet. A significant interaction ( P =0.035) with the randomized diet was observed for rs7903146 and change in lean mass at 6 months. No significant associations were observed at 2 years. Conclusion: In conclusion, overweight/obese individuals with the risk genotype of TCF7L2 rs12255372 may reduce their body mass and adiposity by following a diet lower in total fat.