TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight-loss intervention123

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Background:TCF7L2 gene variants have been associated with increased risk of type 2 diabetes and higher adiposity. Observational studies and short-term trials have suggested that macronutrients may modify these effects. However, to our knowledge, this has yet to be verified in long-term interventions.

Objective: In a long-term intervention setting, we investigated the effects of TCF7L2 polymorphisms rs7903146 and rs12255372 and dietary total fat on changes in body composition and subsequent glycemic control.

Design: Data were analyzed for 591 participants in the Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial, which is a 2-y weight-loss randomized clinical trial of diets that differed in macronutrient proportions. Adjusted means for changes in body composition at 6 and 24 mo were obtained for gene main effects and interactions with a low-fat diet (20% from energy) compared with a high-fat diet (40% from energy). Interactions with protein and carbohydrate intakes were also tested. Predicted changes in glycemic control from changes in adiposity were determined by genotype and diet type.

Results: Significant interactions were observed for rs12255372 TT (risk genotype) and fat intake for changes in BMI, total fat mass, and trunk fat mass (all P/q < 0.05) at 6 mo, with nonsignificant larger decreases for TT carriers on a low-fat diet. No significant associations were observed at 24 mo or for other macronutrients. Changes in body composition for TT carriers predicted reductions in plasma glucose and insulin only on the low-fat diet.

Conclusions: Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposity by consuming a diet lower in total fat. These reductions may induce better glycemic control for such individuals predisposed to type 2 diabetes. The Pounds Lost trial was registered at clinicaltrials.gov as NCT00072995.

Abbreviations:

DXA
dual-energy X-ray absorptiometry
LD
linkage disequilibrium
Pounds Lost
Preventing Overweight Using Novel Dietary Strategies
SNP
single-nucleotide polymorphism

Cited by (0)

1

From the Department of Nutrition, Harvard School of Public Health, Boston, MA (JM, QQ, FBH, FMS, and LQ), and the Channing Laboratory, Brigham and Women's Hospital, Boston, MA (FBH, FMS, and LQ).

2

Supported by the National Heart, Lung and Blood Institute (NIH grants HL073286 and HL071981), the General Clinical Research Center at the NIH (grant RR-02635), the National Institute for Diabetes and Digestive and Kidney Diseases (grant DK091718), and the Boston Obesity Nutrition Research Center (grant DK46200).

3

Address reprint requests and correspondence to L Qi, Department of Nutrition, Harvard School of Public Health, Building 2, Room 345, 655 Huntington Avenue, Boston, MA 02115. E-mail: [email protected]

Copyright © 2012 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.