Article

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: 13.25). 09/2008; 168(16):1791-7. DOI: 10.1001/archinte.168.16.1791
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ABSTRACT 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.

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    • "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. "
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    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.
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    • "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. "
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    • "620 0.57 AA genotype 285 0.31 106 0.20 AT genotype 430 0.47 254 0.47 TT genotype 197 0.22 183 0.34 2008; Ng et al., 2008; Rampersaud et al., 2008; Tönjes et al., 2008; Villalobos-Comparán et al., 2008; Xi et al., 2010 "
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    ABSTRACT: Several studies have reported an association of the intronic single nucleotide polymorphism (SNP) rs9939609 of the fat mass and obesity-associated (FTO) gene with obesity and with a number of obesity-related features. We studied the association of rs9939609 with obesity in 912 obese children and adolescents (426 males and 486 females, mean ± SD age 10.5 ± 3.3 years) and in 543 normal weight subjects. A number of biochemical and clinical parameters was also evaluated in 700 of these patients. In the obese group, mean body mass index standard deviation score (BMI-SDS) was similar between the three genotypes. The A allele was present in 55% of the patients' and in 43% of controls' chromosomes. The distribution of heterozygotes was similar between patients and controls (47%), while the distribution of AA homozygotes was significantly higher in patients (31% vs. 20%). Logistic regression analysis on the genotypes yielded a χ(2) of 35.5 with an odds ratio of 1.6 (CI = 1.3-1.8), P < 1 × 10(-5) . None of the clinical and metabolic parameters tested was associated with the genotype. In conclusion, we have confirmed the strong association between FTO and obesity, and shown that only AA homozygotes are predisposed to develop obesity while TT homozygotes might be protected. Finally, we found no association between rs9939609 and a number of obesity-related abnormalities.
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