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Am J Clin Nutr. 2009 Nov;90(5):1426-32. doi: 10.3945/ajcn.2009.28053. Epub 2009 Sep 30.

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

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  • 1Department of Human Biology, Maastricht University, Maastricht, Netherlands. m.denhoed@hb.unimaas.nl

Abstract

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.

PMID:
19793853
[PubMed - indexed for MEDLINE]
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