title: The fat-mass and obesity-associated (FTO) gene, physical activity, and risk of incident cardiovascular events in white women.
abstract: BACKGROUND
  Variation in the Fat-Mass and Obesity-Associated (FTO) gene has been associated with obesity, diabetes, and hypertension. However, its association with cardiovascular disease (CVD) in healthy populations and any interaction with physical activity remain unclear.
  
  
  METHODS
  The FTO rs8050136 allele was determined in a prospective cohort study of 21,674 apparently healthy White US women in the Women's Genome Health Study.
  
  
  RESULTS
  During a mean follow-up of 12.7±2.0 years, 664 incident CVD events occurred. The risk allele (A) was associated with higher prevalence of hypertension, diabetes, and metabolic syndrome (all P<.05). In a multivariate model, there was significant association of the risk allele with CVD (hazard ratio [HR] per allele copy 1.14, 95% CI 1.01-1.28) that was no longer significant after additional adjustment for body mass index (BMI) (HR 1.10, 95% CI 0.97-1.23). There was statistical evidence of an interaction between FTO and physical activity (P=.048). We found a significant association of FTO with CVD only among less-active (≤8.8 metabolic equivalent-h/wk) women (HR 1.19, 95% CI 1.02-1.38) in multivariate analyses that included BMI. More-active women did not have this increased risk (HR 0.96, 95% CI 0.79-1.16]). In a model that adjusted for BMI, less-active/high-risk (A/A) women were at 54% increased risk of developing CVD (HR 1.54, 95% CI 1.13-2.11), compared to more-active/low-risk (C/C) women.
  
  
  CONCLUSIONS
  Carriers of the FTO risk allele have an increased risk of CVD mediated by BMI. There appears to be an interaction with physical activity, such that this risk increase is only in less-active women.
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Samia
authors.initials: S
authors.lastname: Mora
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
mesh_terms: D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001241:Aspirin / Q000627:therapeutic use; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D010975:Platelet Aggregation Inhibitors; D011506:Proteins; D004247:DNA; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D001241:Aspirin