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Born to run? UAB studies influence of genes on exercise

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  • December 15, 2010

Almost every cell in your body contains DNA — the set of master instructions that directs development, bodily functions and even behavior. Though the DNA of all humans is more than 99 percent identical, the differing percentage produces a variety of sizes, shapes, colors and faces.

mollY_bray_webThese small differences in the DNA sequence influence, at least in part, the reason people look different, have differing risks for some diseases and conditions and respond differently to the same medical treatment or training program.  

Although we know that genes are important in our overall fitness, the ways in which they alter response to exercise and diet interventions are not known. A five-year study coming to UAB in January 2011 hopes to incorporate the exercise patterns of 3,200 students to bring further understanding of the reasons individuals respond and/or persist in exercise and formulate better and more efficacious interventions for obesity.

The TIGER (Training Interventions & Genetics of Exercise Response) Study will investigate the influence of variation in DNA sequence on body fatness and fitness, both prior to and following a 35-week exercise program. The groundbreaking study is one of the few of its kind in the United States.

Molly Bray, Ph.D., a professor of epidemiology in the UAB School of Public Health, is the principal investigator for the five-year, $3.5 million Phase II study funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The first phase of the study began in 2003 at the University of Houston and identified preliminary associations between gene variation and exercise dropout. Almost 2,000 University of Houston students have participated in the study to date. Now UAB students will have the opportunity to participate in Phase II, which will build on these observations in three primary areas:

  • Formal evaluation of the TIGER Study intervention protocol to achieve long-term change in the participants
  • Investigation of gene-expression patterns as a strategy for identifying genes related to exercise response
  • Investigation of the association between genetic variation and exercise adherence

Subjects will undergo 35 weeks of exercise training; then six, 12 and 24 months after completing the study protocol they will be contacted and questioned about their current exercise habits and body weight.

“The recommendations for exercise seem to change frequently, but we’re showing that people see more results when they work out harder,” Bray says. “They don’t have to work out as long that way, and they are more likely to stick with the program. That’s exercise adherence. Everyone knows you will lose weight if you diet and exercise. The hardest part of that equation is doing it.”

That’s where Bray believes genes come into play. Research has shown that the FTO gene has been associated most robustly with obesity. TIGER research shows the gene also is associated strongly with exercise adherence.

“We want to answer the question of whether or not genes, gene variation and DNA sequence predict whether or not people persist in exercise following the completion of a formalized exercise program,” Bray says.

The National Human Genome Research Institute has contacted Bray to express its interest in the TIGER Study.

In addition to understanding the role genes play in changing our physiology, researchers are becoming more interested in the possibility that genes change our behavior.

“Imagine if we knew something about the genetic makeup of people prior to giving them the generic ‘you need to exercise, diet and lose weight,’ mantra,” Bray says. “Both physicians and patients feel frustrated when this standard recommendation doesn’t work. But if our genetic makeup influences our behavior, knowing a person’s DNA sequence in genes related to exercise adherence may help the physician to select the type of program that is most likely to produce positive results for each individual.

“This kind of idea sounds far-fetched until one considers that, at one time, no one knew the predictive value of a cholesterol measure, something now routinely tested as part of health screening,” she says.

Unique study

Several other aspects make this study unique.

First, UAB students ages 18-30 can be involved directly and receive course credit. The study will follow students who enroll in special sections of the PE 131 Aerobics course. Classes are offered every hour from 7 a.m. to 2 p.m. Monday, Wednesday and Friday. More than 40 students already have enrolled for the spring semester.

Students will meet in the Campus Recreation Center, check out a heart-rate monitor and exercise in their target range for at least 30 minutes each session.

Students will receive a free evaluation of their physical fitness and body composition by the dual-energy X-Ray absorptiometry (DXA scan) and blood test for cholesterol, blood sugar and DNA analysis, plus exercise with fitness experts and instruction on goal setting.

“A large number of 18-year-olds have never been active,” Bray says. “You assume most have been active through playing sports and other activities, but that’s not always the case. Most young adults have never been taught to exercise in a way in which they can tolerate comfortably and see results. That’s one of the best things about this study, aside from the genetics. Students learn how to exercise effectively.”

After students complete the 15-week course, they will continue to have access to the study heart-rate monitor checkout system for the remaining 20 weeks of the study, without having to enroll in a formal class.  

“Some students may say, ‘I suffered through 15 weeks, couldn’t wait until it was over, and I never want to exercise again in my life,’ and maybe part of that is driven by genes,” Bray says. “But I’m also sure there will be some who discover they love it, and it makes them feel and function better. We have lots of anecdotal evidence that shows that can happen, too, and perhaps it’s also driven by genes.”

In addition to collaborating with the Campus Recreation Center, several UAB faculty have joined Bray and will be part of the TIGER Study. Jamy Ard, M.D., associate professor of nutrition sciences, will provide medical oversight. Jose Fernandez, Ph.D., associate professor of nutrition sciences and expert on obesity, also is part of the team, as is Gary Hunter, Ph.D., professor of health education and expert in exercise physiology.

“This is really a fun opportunity for me and, I believe, for our students,” says Bray, who came to UAB in September 2009 from the Baylor College of Medicine. “I’m excited to see this study coming to UAB and to add the expertise of the other UAB faculty to this project. Each one of the investigators involved is top notch in their area of expertise.”

Visit www.tigerstudy.org for more information, or e-mail tigerstudy@uab.edu or call 975-7651.