title: Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study.
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.
  
  
  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.
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Québec, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Do
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.forename: Katia
authors.initials: K
authors.lastname: Desbiens
authors.forename: Alexandre
authors.initials: A
authors.lastname: Belisle
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D015519:Bone Density; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D014644:Genetic Variation; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D011792:Quebec
chemical_list: D020738:Leptin; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human