Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study

  1. Ron Do1,
  2. Swneke D. Bailey1,
  3. Katia Desbiens2,
  4. Alexandre Belisle3,
  5. Alexandre Montpetit3,
  6. Claude Bouchard4,
  7. Louis Pérusse56,
  8. Marie-Claude Vohl67 and
  9. James C. Engert1268
  1. 1Department of Human Genetics, McGill University, Montréal, Québec, Canada
  2. 2Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
  3. 3McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
  4. 4Pennington Biomedical Research Center, Baton Rouge, Louisiana
  5. 5Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
  6. 6Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
  7. 7Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
  8. 8Department of Medicine, McGill University, Montréal, Québec, Canada
  1. Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca

Abstract

OBJECTIVE—A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity. Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and expenditure.

RESEARCH DESIGN AND METHODS—We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term study of extensively phenotyped individuals designed to investigate factors involved in adiposity.

RESULTS—We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated with BMI (P = 0.0014), weight (P = 0.0059), and waist circumference (P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin (P = 0.011), homeostasis model assessment of insulin resistance (P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test (P = 0.0091). Associations were also found with resting metabolic rate (RMR) (P = 0.042) and plasma leptin levels (P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels.

CONCLUSIONS—These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-1267.

  • Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1267.

  • 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 January 14, 2008.
    • Received September 6, 2007.
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  1. Published online before print March 3, 2008, doi: 10.2337/db07-1267 Diabetes April 2008 vol. 57 no. 4 1147-1150
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