Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity

Department of Medicine, University of Maryland, Baltimore, USA. .
Archives of internal medicine (Impact Factor: 17.33). 09/2008; 168(16):1791-7. DOI: 10.1001/archinte.168.16.1791
Source: PubMed


Common FTO (fat mass and obesity associated) gene variants have recently been associated with body mass index (BMI) and obesity in several large studies. The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown.
To determine if FTO variants are associated with BMI in Old Order Amish (OOA) individuals, and to further determine whether the detrimental associations of FTO gene variants can be lessened by increased physical activity, a total of 704 healthy OOA adults were selected from the Heredity and Phenotype Intervention (HAPI) Heart Study, an investigation of gene x environment interactions in cardiovascular disease, for whom objective quantified physical activity measurements were available and for whom 92 single-nucleotide polymorphisms (SNPs) in FTO were genotyped.
Twenty-six FTO SNPs were associated with BMI (P = .04 to <.001), including rs1477196 (P < .001) and rs1861868 (P < .001), 2 SNPs in moderate linkage disequilibrium in the OOA (D' = 0.82; r(2) = 0.36). Stratified analyses of rs1861868 revealed its association with BMI to be restricted entirely to those subjects with low sex- and age-adjusted physical activity scores (P < .001); in contrast, the SNP had no effect on those with above-average physical activity scores (P = .29), with the genotype x physical activity interaction achieving statistical significance (P = .01). Similar evidence for interaction was also obtained for rs1477196.
Our results strongly suggest that the increased risk of obesity owing to genetic susceptibility by FTO variants can be blunted through physical activity. These findings emphasize the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals.

Download full-text


Available from: Braxton D Mitchell
  • Source
    • "Obesity is also just as clearly a genetic disease, because all available data suggest that 60–80% of the observed variance in human body weight can be accounted for by inherited factors (Wardle, Carnell, Haworth, & Plomin, 2008). Finally, there is good evidence for gene × environment interactions for obesity risk alleles (Ahmad et al., 2011; Andreasen et al., 2008; Demerath et al., 2013; Garver et al., 2013; Qi et al., 2012; Rampersaud et al., 2008; Rosenquist et al., 2015). Thus, for obesity, " genetic background loads the gun, but the environment pulls the trigger " (Bray, 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of child and adolescent obesity in the United States increased dramatically between 1970 and 2000, and there are few indications that the rates of childhood obesity are decreasing. Obesity is associated with myriad medical, psychological, and neurocognitive abnormalities that impact children's health and quality of life. Genotypic variation is important in determining the susceptibility of individual children to undue gains in adiposity; however, the rapid increase in pediatric obesity prevalence suggests changes to children's environments and/or to their learned behaviors may dramatically affect body weight regulation. This paper presents an overview of the epidemiology, consequences, and etiopathogenesis of pediatric obesity, serving as a general introduction to the subsequent papers in this Special Issue that address aspects of childhood obesity and cognition in detail. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Mar 2015 · Appetite
  • Source
    • "Several recent studies suggested that physical activity (PA) may attenuate the influence of genetic factors on development of obesity. The most extensively analyzed example of a gene interaction with PA in obesity is for the FTO locus, with various studies concluding in general that physical inactivity accentuates the influence of FTO variants on obesity-related traits (Andreasen et al., 2008; Rampersaud et al., 2008; Ruiz et al., 2010; Xi et al., 2011). However, this gene versus PA interaction in obesity has not yet been assessed in a young adult population. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate in a population sample of Portuguese young adults the association of the FTO variant rs9939609 with obesity, BMI, and body-fat and interaction with physical activity (PA) on obesity-susceptibility. SNP rs9939609 A/T was genotyped in 550 subjects (231 males and 319 females; 18-36 years old; mean age 21 years old) by TaqMan assay. PA was assessed with a validated self-reported questionnaire of IPAQ. We replicated the association of rs9939609-A risk allele with BMI (P = 0.04) and fat-mass (P = 0.031), and with overweight (including obesity) under a recessive model (P = 0.034). Stratified analyses showed (i) a significant association with overweight/obesity in inactive individuals (P = 0.02) but not in a group reporting participation in sports (P = 0.97). Spearman's correlation test suggested that the impact of a successive increase in PA was a decrease in the body-fat percentage (r = -0.16; P = 0.0002), which is accentuated for homozygous AA (r = -0.34; P = 0.002), and an increase in BMI (r = 0.14; P = 0.001), with a statistically significant correlation for homozygous TT (r = 0.22; P = 0.002). This study reveals interactions between rs9939609 and PA on obesity indices in Portuguese young adults, suggesting a change in the different body components (lean and fat mass) depending on the FTO genotypes. Am. J. Hum. Biol., 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · American Journal of Human Biology
  • Source
    • "For example, common variants in the FTO obesity gene are associated with increased BMI in populations of sedentary Caucasians. However, the association is either blunted or absent in physically active groups (Rampersaud et al. 2008; Ahmad et al. 2013). There is hope that whole genome sequencing of large numbers of humans will provide more insight into genotype–phenotype relationships for common diseases, but skepticism about what additional insights are possible is understandable given that so little has come from genome-wide association studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype–phenotype relationship in humans, (2) the common-disease–common-variant hypothesis, (3) the current ability of ‘omic’ information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to ‘stop chasing Mendel?’
    Preview · Article · Jun 2014 · The Journal of Physiology
Show more