The common single-nucleotide polymorphism in the FTO (fat mass and obesity associated) gene is consistently associated with an increased risk of obesity. However, the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited. We examined whether the FTO gene variant (rs9939609, T/A) is associated with body weight and BMI and long-term weight changes in the Finnish Diabetes Prevention Study (DPS). Altogether, 522 (aged 40-65 years; BMI >or=25 kg/m(2)) subjects with impaired glucose tolerance (IGT) were randomized to control and lifestyle intervention groups. SNP rs9939609 was genotyped from 502 subjects. At baseline, those with the AA genotype had higher BMI than subjects with other genotypes (P = 0.006). The association was observed in women (P = 0.016) but not in men. During the 4-year follow-up, the subjects with the AA genotype had consistently the highest BMI (P = 0.009) in the entire study population. The magnitude of weight reduction was greater in the intervention group, but the risk allele did not modify weight change in either of the groups. Our results confirm the association between the common FTO variant and BMI in a cross-sectional setting and during the long-term lifestyle intervention. We did not observe association between FTO variant and the magnitude of weight reduction achieved by long-term lifestyle intervention. Based on the results from the DPS, it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss.
Lappalainen, T. J., Tolppanen, A. M., Kolehmainen, M., Schwab, U., Lindström, J., Tuomilehto, J., … Uusitupa, M. (2009). The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: The finnish diabetes prevention study. Obesity, 17(4), 832–836. https://doi.org/10.1038/oby.2008.618