Effects of FTO genotype on weight loss and metabolic risk factors in response to calorie restriction among Japanese women.

Effects of gene variants in the fat-mass and obesity-associated (FTO) gene (primarily rs9939609) on weight loss induced by lifestyle intervention are controversial. The aim of this study was to investigate whether FTO gene variations are associated with weight-reduction and changes in metabolic risk factors in response to a 14-week calorie restriction. In total, 204 Japanese women (aged 24-66 years; BMI ≥ 25 kg/m(2)) enrolled as subjects and attended dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Fat mass, both at baseline (P = 0.100) and after the intervention (P = 0.020), was higher in subjects with the AA genotype (n = 15; 7.3%) than in those with TT (n = 114; 55.9%) and TA (n = 75; 36.8%) genotypes. The change in fat-mass tended to be smaller in subjects with the AA genotype than in those with other genotypes (P = 0.065). However, the subjects with the risk allele could still decrease their body weight and improve metabolic risk factors significantly. Our data suggest that the impact of FTO rs9939609 in Japanese women may not be great enough to change body weight or metabolic risk factors in response to calorie restriction. Environmental and behavioral factors may overcome the effects of genes on weight reduction.