title: FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness.
abstract: BACKGROUND
  A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.
  
  
  RESULTS
  Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2)) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6), OR = 1.20, p = 1.7*10(-7), OR = 1.17, p = 3.4*10(-3), respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7) and OR = 1.21, p = 1.0*10(-3)). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6) and OR = 1.19, p = 5.9*10(-3)), sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4) and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5) and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.
  
  
  CONCLUSIONS
  The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat.
authors.affiliation: Institute of Preventive Medicine, Copenhagen University Hospitals, Centre for Health and Society, Copenhagen, Denmark. si@ipm.regionh.dk
authors.forename: Sofia I I
authors.initials: SI
authors.lastname: Kring
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Esther
authors.initials: E
authors.lastname: Zimmermann
authors.forename: Tine
authors.initials: T
authors.lastname: Jess
authors.forename: Tina
authors.initials: T
authors.lastname: Berentzen
authors.forename: Søren
authors.initials: S
authors.lastname: Toubro
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000145:classification / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D050177:Overweight / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D008076:Cholesterol, HDL; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human