For people who have a genetic mutation that predisposes them to a high body mass index (BMI), physical activity may be a way for them to reduce their heightened risk for obesity. These findings are published in the September 8 issue of Archives of Internal Medicine.

Researchers and medical professionals have acknowledged that there exists a genetic component to BMI and obesity. In fact, the fat mass and obesity associated (FTO) gene variant has recently been shown to have a strong association with BMI. These gene mutations that are linked to obesity exists in some 30% of European populations and can lead to an about 3.9 pounds (1.75-kilogram) increase in body weight. Although additional contributions to weight gain relate to lifestyle factors such as diet and physical activity, it is now well understood how these factors affect or are affected by genetics.

This recent study, conducted by Evadnie Rampersaud, M.S.P.H., Ph.D. (University of Miami, but formerly of the University of Maryland School of Medicine in Baltimore) and colleagues, included DNA analyses of 704 healthy Amish adults. The participants, about 43.6 years old and 53% men, were recruited from 2003 to 2007. In addition to a series of physiological tests, participants had physical activity monitored for seven days using an accelerometer.

The researchers found that 54% of men and 63.7% of women were overweight, with 10.1% of men and 30.5% of women classified as obese. The genetic analysis revealed that 26 single-nucleotide polymorphisms (SNPs – single base letter changes in DNA) in the FTO gene were linked with BMI.

After separating the participants into two groups that reflected physical activity levels, Rampersaud and colleagues studied the relationship between BMI and the two strongest SNPs. Only in individuals with low physical activity scores for age and sex were both SNPs associated with BMI. That is, the SNPs seemed to have no effect on individuals with above-average physical activity scores.

The authors clarify that, “Activity levels in the ‘high-activity’ stratum were approximately 900 calories [860 calories for women and 980 calories for men] higher than in the ‘low-activity’ stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening.”

“We have replicated the associations of common SNPs in the FTO gene with increased BMI and risk to obesity in the Old Order Amish,” conclude the researchers. “Furthermore, we provide quantitative data to show that the weight increase resulting from the presence of these SNPs is much smaller and not statistically significant in subjects who are very physically active. This finding offers some clues to the mechanism by which FTO influences changes in BMI and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals.”

Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity
Evadnie Rampersaud; Braxton D. Mitchell; Toni I. Pollin; Mao Fu; Haiqing Shen; Jeffery R. O’Connell; Julie L. Ducharme; Scott Hines; Paul Sack; Rosalie Naglieri; Alan R. Shuldiner; Soren Snitker
Arch Intern Med. (2008). 168(16):1791-1797.
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Written by: Peter M Crosta