Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity.
BACKGROUND
A common variant in the first intron of FTO (rs9939609, T/A) is associated with fatness in Caucasians.


OBJECTIVE
FTO may regulate energy homeostasis through the hypothalamus, and we hypothesized that AA-genotypes of rs9939609 FTO have lower energy expenditure and/or a lower level of physical activity.


METHODS
The study population included all obese young men (body mass index > or = 31 kg/m(2)) at the mandatory draft board examinations in the Copenhagen area from 1943 to 1977 and a randomly selected control group from this population. Subgroups of 234 obese and 323 controls were examined in 1998-2000 (median age 48 yr). Fat mass (FM), lean body mass (LBM), leisure-time physical activity (LTPA), maximum oxygen uptake (VO(2)max), resting energy expenditure (REE), and glucose-induced thermogenesis (GIT) were measured. The FTO rs9939609 variant was genotyped. A recessive transmission mode fit the data best. Logistic regression was used to assess the odds ratios of the AA-genotype in relation to LTPA, VO(2)max, REE, and GIT.


RESULTS
The AA-genotype of FTO rs9939609 had higher REE in the age-adjusted model, but the association was eliminated when adjusting for FM and LBM. The AA-genotype was not associated with LTPA, VO(2)max, or GIT. This was not influenced by adjustment for age, FM, or LBM. The AA-genotype had increased FM, even with adjustment for age, LBM, REE, GIT, VO(2)max, and LTPA. Results were similar for FTO rs8050136 and rs7193144.


CONCLUSIONS
Homozygous carriers of the A-allele of rs9939609 FTO do not have lower REE, GIT, VO(2)max, or LTPA but higher FM, irrespective of LBM, REE, GIT, VO(2)max, and LTPA.
Berentzen
T
T
Institute of Preventive Medicine, Øster Søgade 18, Copenhagen K, Denmark. tb@ipm.regionh.dk
Kring
S I I
SI
Holst
C
C
Zimmermann
E
E
Jess
T
T
Hansen
T
T
Pedersen
O
O
Toubro
S
S
Astrup
A
A
Sørensen
T I A
TI
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D004734:Energy Metabolism; D015444:Exercise; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011506:Proteins / Q000235:genetics*; D022722:Thermogenesis
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human