The fat-mass and obesity-associated (FTO) gene, physical activity, and risk of incident cardiovascular events in white women

Am Heart J. 2010 Dec;160(6):1163-9. doi: 10.1016/j.ahj.2010.08.002.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Aspirin / therapeutic use
  • Body Mass Index
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / prevention & control
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genotype
  • Humans
  • Middle Aged
  • Motor Activity / physiology*
  • Obesity / genetics
  • Obesity / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prospective Studies
  • Proteins / genetics*
  • Proteins / metabolism
  • Reference Values
  • Risk Factors
  • Surveys and Questionnaires


  • Platelet Aggregation Inhibitors
  • Proteins
  • DNA
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Aspirin