Training vs. genetics

Intrigued by differences in athletic ability, one researcher finds that a certain muscle protein plays a role in cardiovascular fitness.

July 2015

As a former competitive cyclist, Dustin Hittel was always intrigued by how some people were naturally gifted athletes while others floundered, often with the same training. “I was always a great climber but couldn’t sprint to save my life,” he recalls with a laugh.

So in 2003, when researchers established a link between muscle power, elite-level athletics, and a muscle protein called actinin-3, Hittel was more than a little intrigued. Since then, scientists have been trying to understand the mechanisms of actinin-3 or ACTN3 — dubbed “the sports gene.” About a billion people worldwide appear to carry two mutant copies of the gene, resulting in the complete absence of this protein in their muscle.

Fast-forward 10 years. In his lab, Hittel, PhD, was looking for genes related to the development of obesity and type 2 diabetes in healthy young adults. Hittel had enrolled 250 students from the University of Calgary to participate in a study, using mouth swabs to analyze and sequence the students’ genes. Hittel is a researcher at the University of Calgary Cumming School of Medicine, and member of the Alberta Children’s Hospital Research Institute and Libin Cardiovascular Institute of Alberta.

“It’s the first time the protein has been unambiguously associated with cardio metabolic fitness."

That’s when he was unexpectedly reintroduced to ACTN3. Hittel found that people with two copies of the ACTN3 mutation (one in five people) have higher body weight and reduced fitness as measured by a maximum oxygen consumption test. Hittel also found alpha actinin-3 in an unexpected place: in the muscle surrounding the pulmonary vein that delivers unoxygenated blood to the lungs from the heart.

His research extended the role of this protein beyond elite athlete populations and identified for the first time an important role for the protein in oxygen metabolism and cardiovascular fitness. “It’s the first time the protein has been unambiguously associated with cardio metabolic fitness in humans,” he says. “It was quite a moment when we learned what we had discovered.”

The research paper, “The ACTN3 R577X Polymorphism is Associated with Cardiometabolic Fitness in Healthy Young Adults,” has been published in the online journal PLOS One.

While the clinical implications of this finding need to be explored in more detail, recent evidence has emerged linking ACTN3 to heart failure. Hittel says future research could study the role of the protein in heart failure, the protein’s presence in different elite populations at the University of Calgary, and the evolutionary role of the protein and how it shapes modern disease.

“I am so proud that we are able to conduct this type of world-class genomics research in Calgary," says Hittel.


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