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

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. International Journal of Obesity ( 2010) 34, 266-272; doi: 10.1038/ijo.2009.233; published online 17 November 2009