A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes

Int J Obes (Lond). 2010 Feb;34(2):266-72. doi: 10.1038/ijo.2009.233. Epub 2009 Nov 17.


Introduction: The aim of this study was to analyze the effects of the rs9939609 (T/A) gene variant in fat mass and obesity-associated gene (FTO) on body weight changes after 3 years and its modification by a randomized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk.

Design: A substudy of PREDIMED, which is a randomized trial aimed at assessing the effect of the Mediterranean diet (MD) for primary cardiovascular disease prevention. There were three nutritional intervention groups: two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet.

Subjects: A total of 776 high cardiovascular risk subjects aged 55-80 years.

Measurements: Anthropometric measurements were recorded at baseline and at 3 years. The participants were genotyped by RT-PCR, followed by allelic discrimination.

Results: Homozygous subjects had the highest baseline body weight. The dominant model showed that subjects carrying the A allele had the lowest body weight gain (B=-0.685; P=0.022) after 3 years of nutritional intervention compared with nonmutated subjects (TT genotype) regardless of the nutritional intervention. Moreover, this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups (B=-0.830; P=0.018), but it was not significant among those allocated to the control group (P for interaction=0.649).

Conclusion: This study confirmed the association between body weight and the FTO rs9939609 polymorphism. Interestingly, our results showed that, although at baseline the A allele was associated with higher body weight, after 3 years of nutritional intervention with a Mediterranean-style-diet, A-allele carriers had lower body weight gain than wild type subjects. No interaction between nutritional intervention and the polymorphism was found.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index
  • Body Weight / genetics*
  • Cardiovascular Diseases / diet therapy
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / prevention & control
  • Diet, Fat-Restricted
  • Diet, Mediterranean*
  • Female
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / genetics*
  • Proteins / genetics*
  • Time Factors
  • Treatment Outcome
  • Weight Gain / genetics


  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human