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.


METHODS
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.
den Hoed
Marcel
M
Department of Human Biology, Maastricht University, Maastricht, Netherlands. m.denhoed@hb.unimaas.nl
Westerterp-Plantenga
Margriet S
MS
Bouwman
Freek G
FG
Mariman
Edwin C M
EC
Westerterp
Klaas R
KR
D000293:Adolescent; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002353:Carrier State; D003463:Cues; D019175:DNA Methylation / Q000235:genetics; D004435:Eating; D002149:Energy Intake; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D006815:Hunger / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D012528:Satiety Response / Q000502:physiology*; D055815:Young Adult
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human