Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity

Background: The fat mass and obesity-associated gene (FTO) has been shown to be associated with obesity and to influence appetite regulation. Objective: The aim was to examine whether dietary factors (macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m(2)). Design: A cross-sectional study examined 4839 subjects in the population-based Malmo Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO ( rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities. Results: Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 ( 95% CI: 25.8, 26.8) among AA carriers ( P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes ( BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity ( P for trend = 0.004, P for interaction = 0.05). Conclusion: Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant. Am J Clin Nutr 2009;90:1418-25.