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: 6.92). 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.

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    • "The pathways by which these genetic variants contribute to obesity are not yet understood but there is some evidence that the effects of variants in FTO are modified by energy imbalance [11] [12] [13] [14]. Several studies have shown that increases in body mass index (BMI) per risk allele are lower in people who engage in high levels of physical activity compared to less active people [11] [12] [15]. FTO has also been shown to be associated with dietary fat intake and overall energy consumption [13, 16–18]. "
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    ABSTRACT: Few studies have investigated the association between genetic variation and obesity traits in Indian populations or the role of environmental factors as modifiers of these relationships. In the context of rapid urbanisation, resulting in significant lifestyle changes, understanding the aetiology of obesity is important. We investigated associations of FTO and MC4R variants with obesity traits in 3390 sibling pairs from four Indian cities, most of whom were discordant for current dwelling (rural or urban). The FTO variant rs9939609 predicted increased weight (0.09 Z-scores, 95% CI: 0.03, 0.15) and BMI (0.08 Z-scores, 95% CI: 0.02, 0.14). The MC4R variant rs17782313 was weakly associated with weight and hip circumference (P < .05). There was some indication that the association between FTO and weight was stronger in urban than that in rural dwellers (P for interaction = .03), but no evidence for effect modification by diet or physical activity. Further studies are needed to investigate ways in which urban environment may modify genetic risk of obesity.
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    • "Physical activity is associated with numerous physical and psychological health benefits including: lower rates of type II diabetes (Vimaleswaran et al., 2009), heart disease (Katzmarzyk, Church, & Blair, 2004; Katzmarzyk & Janssen, 2004), and some forms of cancer (McNeely et al., 2006) as well as lower rates of depression and anxiety, and increased positive mood (Scully, Kremer, Meade, Graham, & Dudgeon, 1998). Despite the extensive list of health benefits associated with physical activity, more than half of adults do not meet the minimum weekly recommendations for physical activity (e.g. "
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    Applied Psychology Health and Well-Being 02/2011; 3(1):107 - 126. DOI:10.1111/j.1758-0854.2010.01043.x · 1.75 Impact Factor
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    • "Thus, Mitchell et al. (2009), found that the A allele of rs8050136 gene variant was associated with higher BMI at baseline, but after following the physical activity recommendations of the intervention program, AA subjects were found to have a higher weight loss in comparison to CC subjects [77]. In the EPIC- Norfolk cohort, Vimaleswaran et al (2009), found that T risk allele of rs1121980 was associated with BMI and waist circumference, but physical activity level was able to attenuate this effect [78]. Moreover, Rampersaud et al (2008), found that two FTO gene variants, rs1477196 and rs1861868, were associated with BMI and obesity only in those subjects with a low level of physical activity [79] (Table 5). "
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