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Original Article
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Volume 359:2558-2566 December 11, 2008 Number 24
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An Obesity-Associated FTO Gene Variant and Increased Energy Intake in Children
Joanne E. Cecil, Ph.D., Roger Tavendale, Ph.D., Peter Watt, Ph.D., Marion M. Hetherington, Ph.D., and Colin N.A. Palmer, Ph.D.

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ABSTRACT

Background Variation in the fat mass and obesity–associated (FTO) gene has provided the most robust associations with common obesity to date. However, the role of FTO variants in modulating specific components of energy balance is unknown.

Methods We studied 2726 Scottish children, 4 to 10 years of age, who underwent genotyping for FTO variant rs9939609 and were measured for height and weight. A subsample of 97 children was examined for possible association of the FTO variant with adiposity, energy expenditure, and food intake.

Results In the total study group and the subsample, the A allele of rs9939609 was associated with increased weight (P=0.003 and P=0.049, respectively) and body-mass index (P=0.003 and P=0.03, respectively). In the intensively phenotyped subsample, the A allele was also associated with increased fat mass (P=0.01) but not with lean mass. Although total and resting energy expenditures were increased in children with the A allele (P=0.009 and P=0.03, respectively), resting energy expenditure was identical to that predicted for the age and weight of the child, indicating that there is no defect in metabolic adaptation to obesity in persons bearing the risk-associated allele. The A allele was associated with increased energy intake (P=0.006) independently of body weight. In contrast, the weight of food ingested by children who had the allele was similar to that in children who did not have the allele (P=0.82).

Conclusions The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods.


Source Information

From the Bute Medical School, University of St Andrews, St Andrews (J.E.C.); the Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee (R.T., C.N.A.P.); Chelsea School, University of Brighton, Brighton (P.W.); and the Department of Psychology, Glasgow Caledonian University, Glasgow (M.M.H.) — all in the United Kingdom.

Address reprint requests to Dr. Palmer at the Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Scotland DD1 9SY, United Kingdom, or at nuclear-receptor{at}dundee.ac.uk.

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Related Letters:

Obesity, FTO Gene Variant, and Energy Intake in Children
Jonsson A., Franks P. W., Palmer C. N.A., Cecil J., Hetherington M.
Extract | Full Text | PDF  
N Engl J Med 2009; 360:1571-1572, Apr 9, 2009. Correspondence

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