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.
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.
Authors: Sungshim Lani Park; Iona Cheng; Sarah A Pendergrass; Anna M Kucharska-Newton; Unhee Lim; Jose Luis Ambite; Christian P Caberto; Kristine R Monroe; Fredrick Schumacher; Lucia A Hindorff; Matthew T Oetjens; Sarah Wilson; Robert J Goodloe; Shelly-Ann Love; Brian E Henderson; Laurence N Kolonel; Christopher A Haiman; Dana C Crawford; Kari E North; Gerardo Heiss; Marylyn D Ritchie; Lynne R Wilkens; Loïc Le Marchand Journal: Am J Epidemiol Date: 2013-07-02 Impact factor: 4.897
Authors: C Holzapfel; H Grallert; C Huth; S Wahl; B Fischer; A Döring; I M Rückert; A Hinney; J Hebebrand; H-E Wichmann; H Hauner; T Illig; I M Heid Journal: Int J Obes (Lond) Date: 2010-04-13 Impact factor: 5.095
Authors: George Stratigopoulos; Jayne F Martin Carli; Diana R O'Day; Liheng Wang; Charles A Leduc; Patricia Lanzano; Wendy K Chung; Michael Rosenbaum; Dieter Egli; Daniel A Doherty; Rudolph L Leibel Journal: Cell Metab Date: 2014-05-06 Impact factor: 27.287
Authors: William S Garver; Sara B Newman; Diana M Gonzales-Pacheco; Joseph J Castillo; David Jelinek; Randall A Heidenreich; Robert A Orlando Journal: Genes Nutr Date: 2013-03-08 Impact factor: 5.523
Authors: Yi-Chun Loraine Tung; Eduard Ayuso; Xiaoye Shan; Fatima Bosch; Stephen O'Rahilly; Anthony P Coll; Giles S H Yeo Journal: PLoS One Date: 2010-01-19 Impact factor: 3.240