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Physical Activity Helps Offset Genetic Risk for Obesity 

Individuals who have a genetic mutation associated with high body mass index (BMI) may be able to offset their increased risk for obesity through physical activity, according to the results of a study.

 "Common FTO (fat mass and obesity associated) gene variants have recently been associated with…BMI and obesity in several large studies," write Evadnie Rampersaud, MSPH, PhD, from the University of Maryland in Baltimore, and colleagues. "The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown."

The goal of this study was to evaluate the association of FTO variants with BMI in Old Order Amish individuals and to examine whether the detrimental associations of FTO gene variants could be reduced by increased physical activity. The investigators selected 704 healthy Old Order Amish adults from the Heredity and Phenotype Intervention Heart Study, which was designed to assess interactions between genes and environment in cardiovascular disease. Participants had objective, quantified measurements of physical activity and genotyping of 92 single-nucleotide polymorphisms in FTO.

There were 26 FTO single-nucleotide polymorphisms identified that were associated with BMI (P = .04 to P < .001), including rs1477196 (P <.001) and rs1861868 (P <.001), which are 2 single-nucleotide polymorphisms in moderate linkage disequilibrium in the Old Order Amish (D’ = 0.82; r2 = 0.36). Stratified analyses of rs1861868 showed that the association of this single-nucleotide polymorphism with BMI was restricted exclusively to participants who had low sex- and age-adjusted physical activity scores (P < .001). For participants with above-average physical activity scores, this single-nucleotide polymorphism was not linked to BMI (P = .29). The interaction between genotype and physical activity was statistically significant (P = .01) for rs1861868, as it also was 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," the study authors write. "These findings emphasize the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals."

FTO gene variants consist of a group of single-nucleotide polymorphisms that have been associated with increased BMI, higher fat mass, and the presence of obesity in white adults and children. These genetic variants are common, with up to 30% of some European populations identified as genetic carriers. They are also powerful. Each polymorphism is associated with a 1.75-kg increase in body weight. So far, FTO genes have been demonstrated to function in the hypothalamus and within adipose tissue.

Practice Pearls:

  • FTO gene variants are common and have been associated with BMI, fat mass, and the presence of obesity in white adults and children. FTO genes have been identified, which function in the hypothalamus and within adipose tissue.
  • In the current study, FTO gene variants were associated with increased BMI, but these gene variants only increased the risk for obesity in individuals in the lower half of the distribution of physical activity

Arch Intern Med. 2008;168:1791-1797