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: 6.77). 06/2009; 90(2):425-8. DOI: 10.3945/ajcn.2009.27652
Source: PubMed


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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    • "Given the current state of scientific research, these behavioral and environmental factors are modifiable by the individual or society, while the biological factors, such as genetic predispositions, are less subject to modification. However, it is important to acknowledge that the effect of a genetic susceptibility to being overweight or obese is also modifiable by behavioral factors such as a physically active lifestyle [12]. "
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    • "Consistent with our result, recent report revealed that FTO rs9939609 polymorphism did not show a significant effect on antipsychotic-associated weight gain.19) It is suggested that the medications and lifestyle modifications such as physical activity or diet could overcome the genetic predisposition to obesity in patients with schizophrenia.20,21) As most of our patients were hospitalized for long periods and their food intake and exercise were managed according to the institution's rule, environmental interventions could overcome the genetic susceptibility conferred by the FTO genotype. "
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