Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO

Background: The common rs9939609 single nucleotide polymorphism ( SNP) in the fat mass and obesity-associated (FTO) gene is associated with adiposity, possibly by affecting satiety responsiveness. Objective: The objective was to determine whether postprandial responses in hunger and satiety are associated with rs9939609, taking interactions with other relevant candidate genes into account. Design: Sixty-two women and 41 men [age: 31 +/- 14 y; body mass index ( in kg/m(2)): 25.0 +/- 3.1] were genotyped for 5 SNPs in FTO, DNMT1, DNMT3B, LEP, and LEPR. Individuals received fixed meals provided in energy balance. Hunger and satiety were determined pre- and postprandially by using visual analog scales. Results: A general association test showed a significant association between postprandial responses in hunger and satiety with rs9939609 ( P = 0.036 and P = 0.050, respectively). Individuals with low postprandial responses in hunger and satiety were overrepresented among TA/AA carriers in rs9939609 ( FTO) compared with TT carriers ( dominant and additive model: P = 0.013 and P = 0.020, respectively). Moreover, multifactor dimensionality reduction showed significant epistatic interactions for the postprandial decrease in hunger involving rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 ( LEPR). Individuals with a low postprandial decrease in hunger were overrepresented among TA/AA ( dominant), CC/CA ( recessive), and AG/GG ( dominant) carriers in rs9939609 ( FTO), rs992472 ( DNMT3B), and rs1137101 ( LEPR), respectively (n = 39), compared with TT, AA, and/or AA carriers in these SNPs, respectively ( P = 0.00001). Each SNP had an additional effect. Conclusions: Our results confirm a role for FTO in responsiveness to hunger and satiety cues in adults in an experimental setting. The epistatic interaction suggests that DNA methylation, an epigenetic process, affects appetite. Am J Clin Nutr 2009;90:1426-32.