Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation

  1. Camilla H. Andreasen1,
  2. Kirstine L. Stender-Petersen1,
  3. Mette S. Mogensen1,
  4. Signe S. Torekov1,
  5. Lise Wegner1,
  6. Gitte Andersen1,
  7. Arne L. Nielsen1,
  8. Anders Albrechtsen2,
  9. Knut Borch-Johnsen134,
  10. Signe S. Rasmussen1,
  11. Jesper O. Clausen1,
  12. Annelli Sandbæk5,
  13. Torsten Lauritzen5,
  14. Lars Hansen6,
  15. Torben Jørgensen3,
  16. Oluf Pedersen14 and
  17. Torben Hansen1
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark
  3. 3Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  4. 4Faculty of Health Science, University of Aarhus, Aarhus, Denmark
  5. 5Department of General Practice, University of Aarhus, Aarhus, Denmark
  6. 6Science and Medicine, Novo Nordisk, Bagsværd, Denmark
  1. Address correspondence and reprint requests to Camilla H. Andreasen, Steno Diabetes Center, Niels Steensens Vej 1, NLC2.13, DK-2820 Gentofte, Denmark. E-mail: cila{at}novonordisk.com


OBJECTIVE—Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined.

RESEARCH DESIGN AND METHODS—The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups.

RESULTS—In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06–1.20], P = 9 × 10−5). This association was abolished when adjusting for BMI (1.06 [0.97–1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13–1.24], P = 1 × 10−12) and obesity (1.27 [1.20–1.34], P = 2 × 10−16). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 ± 0.3 kg/m2 increase in BMI compared with homozygous T-allele carriers.

CONCLUSIONS—We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.


  • Published ahead of print at http://diabetes.diabetesjournals.org on 17 October 2007. DOI: 10.2337/db07-0910.

    C.H.A. and K.L.S.-P. contributed equally to this article.

    K.B.-J. has received honorarium for invited lectures by Novo Nordisk, Bristol-Myers Squibb, Novartis, Pfizer, Hermedico, and AstraZeneca.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0910.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted October 10, 2007.
    • Received July 4, 2007.
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  1. Diabetes vol. 57 no. 1 95-101
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