Abstract

Context: 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 ≥ 31 kg/m2) 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 (VO2max), 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, VO2max, 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, VO2max, 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, VO2max, 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, VO2max, or LTPA but higher FM, irrespective of LBM, REE, GIT, VO2max, and LTPA.

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