Article

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene.

MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge CB2 0QQ, United Kingdom.
American Journal of Clinical Nutrition (Impact Factor: 6.5). 06/2009; 90(2):425-8. DOI: 10.3945/ajcn.2009.27652
Source: PubMed

ABSTRACT Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity.
We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active.
The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models.
We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals.
Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.

0 Bookmarks
 · 
103 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic processes, defined as heritable changes in gene expression that occur without changes to the DNA sequence, have emerged as a promising area of cardiovascular disease research. Epigenetic information transcends that of the genotype alone and provides for an integrated etiologic picture of cardiovascular disease pathogenesis because of the interaction of the epigenome with the environment. Epigenetic biomarkers, which include DNA methylation, histone modifications, and RNA-based mechanisms, are both modifiable and cell-type specific, which makes them not only responsive to the environment, but also an attractive target for drug development. However, the enthusiasm surrounding possible applications of cardiovascular epigenetics currently outpaces available evidence. In this review, the authors synthesize the evidence linking epigenetic changes with cardiovascular disease, emphasizing the gap between the translational potential and the clinical reality of cardiovascular epigenetics.
    Translational research : the journal of laboratory and clinical medicine. 04/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genome wide association studies undoubtedly linked variants of the fat mass and obesity-associated protein (FTO) to obesity. To date, however, knowledge on the mechanisms coupling variants in the intron of the FTO gene to its expression or enzymatic activity to alter metabolism remain scarce. Until recently, the investigation of the molecular function of FTO had not led to conclusive results concerning the ‘where’, ‘when’ and ’how’ of FTO activity. Finally, since FTO was identified as a RNA modifying enzyme, demethylating N6-methyladenosine on single stranded RNA, novel understanding of the molecular function is gathered. These and other studies suggest the requirement for a further reaching approach to further investigate FTO function, since the phenotype of aberrant FTO function may encompass more than just obesity. Taking these new insights and translating them into appropriate paradigms for functional research in humans may lead to a deeper understanding of the human physiology and disease. This article is part of a Special Issue entitled: From Genome to Function.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 01/2014; · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Aims. Energy expenditure has been negatively correlated with fat accumulation. However, this association is highly variable. In the present study we applied a genotype by environment interaction method to examine the presence of Genotype x by Total Daily Energy Expenditure and Genotype x by Daily Energy Expenditure interactions in the expression of different body composition traits. Methods and Results. A total of 958 subjects from 294 families of The Portuguese Healthy Family Study were included in the analysis. TDEE and DEE were assessed using a physical activity recall. Body fat percentages were measured with a bioelectrical impedance scale. GxTDEE and GxDEE examinations were performed using SOLAR 4.0 software. All BC traits were significantly heritable, with heritabilities ranging from 21% to 34%. The GxTDEE and GxDEE interaction models fitted the data better than the polygenic model for all traits. For all traits, a significant GxTDEE and GxDEE interaction was due to variance heterogeneity among distinct levels of TDEE and DEE. For WC, GxTDEE was also significant due to the genetic correlation function. Conclusions. TDEE and DEE are environmental constraints associated with the expression of individuals' BC genotypes, leading to variability in the phenotypic expression of BC traits.
    BioMed research international. 01/2014; 2014:845207.