International Congress on Abnominal Obesity
Am J Clin Nutr 90: 1426-1432, 2009. First published September 30, 2009; doi:10.3945/ajcn.2009.28053
 American Journal of Clinical Nutrition, doi:10.3945/ajcn.2009.28053
Vol. 90, No. 5, 1426-1432, November 2009
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© 2009 American Society for Clinical Nutrition

ORIGINAL RESEARCH COMMUNICATION

Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO1,2,3

Marcel den Hoed, Margriet S Westerterp-Plantenga, Freek G Bouwman, Edwin CM Mariman and Klaas R Westerterp

1 From the Department of Human Biology, Maastricht University, Maastricht, Netherlands.

2 Supported by Maastricht University.

3 Address correspondence to M den Hoed, PO Box 616, 6200MD Maastricht, Netherlands. E-mail: m.denhoed{at}hb.unimaas.nl.

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/m2): 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.