Weight: What’s a gene got to do with it?

McCaffery close with students
Jeanne McCaffery (left) speaks to students in her research group about their project. (Kevin Noonan / CAHNR photo)

Many factors contribute to weight gain and loss. There are behavioral and environmental aspects, such as what types of food and how much people choose to eat or the amount of physical exercise they get.

Genetics may also be involved, based on past investigations by Department of Allied Health Sciences (AHS) Associate Professor Jeanne McCaffery and other researchers. Genetic variants may influence individual dietary preferences, the ability to lose weight and, possibly, susceptibility to obesity-related health problems.

The genetics of eating behavior and the genetics of weight loss are central to several of McCaffery’s research projects in her fifteen years of continuous National Institutes of Health (NIH) funding. Ultimately, her work may be useful in treating obesity, which is a known risk factor in type 2 diabetes and cardiovascular disease.

The NIH grant

Her current 3-year, $275,000 grant comes from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. The project is called “Salivary Amylase Gene (AMY1) as a Predictor of Weight and Diet in Look AHEAD and DPP.”

Salivary amylase breaks down starches, such as bread, potato and rice, as part of the digestive process. According to McCaffery, the gene that codes salivary amylase, AMY1, is located within a type of genetic variation called a copy number variant. This results in people having between two and eighteen copies of the AMY1 gene in their genome. The number of copies of AMY1 relates to the amount of the amylase enzyme present in saliva. McCaffery and her colleagues want to know if variations of AMY1 are related to starch preference, body weight and diabetes risk in 7,000 individuals of diverse ancestry.

Because of AMY1’s role in breaking down starch, McCaffery said she is interested in knowing if individuals with an AMY1 variant might prefer starchy food or perhaps would benefit from a low-starch diet as part of weight loss. As AMY1 contributes to the breakdown of starch ultimately to glucose, she is also interested in how the variant relates to diabetes risk.

Test subjects are current participants in two large NIH clinical trials to which the AMY1 genotyping has been added for the purposes of this grant. The Look AHEAD (Action for Health in Diabetes) trial has sixteen sites in the United States, and the Diabetes Prevention Program (DPP) has twenty-seven US trial sites.

The UConn researcher and teacher

McCaffery students standing
McCaffery with her eight research group students. First row (from left): Erica Allen, Sophie Nemec, Jeanne McCaffery, Kori Barriteau, Ana Fuentes, Mark Liguori. Second row (from left): David Massabni, Olasubomi (Mini) Ajayi, Lauren Corso. (Kevin Noonan / CAHNR photo)

As a licensed clinical psychologist, McCaffery is interested in the field of cardiovascular behavioral medicine, or how a person’s actions and reactions predict heart disease. Over the course of her career, McCaffery has conducted research on diet and obesity, cigarette smoking and stress. This research uniquely examines the role of these behaviors in the context of genetic risk for obesity, diabetes and heart disease. McCaffery finds that behaviors can improve or worsen genetic risk.

“UConn’s excellent behavioral programs and strong genetics programs put me in a good home for this research,” McCaffery said. In addition to being on the faculty of AHS, she serves as an investigator for both the Institute for Collaboration on Health, Intervention, and Policy and the Institute for Systems Genomics. McCaffery, who came to UConn in 2016, said she enjoys being in a department with such a broad perspective on health promotion and looks forward to continuing to build on her research projects in Connecticut.

AHS department head Professor Justin Nash said, “We are excited to have Dr. McCaffery in the Department of Allied Health Sciences. With her research, she brings uniqueness in the interplay between genetics and unhealthy behavior that contributes to cardiovascular disorders. She also created two instructional offerings in research that have been well received by students. One is a research methods course for honors students, and the other is small group instruction for students who are involved in her research.”

The honors course includes the topics of designing a study, analyzing data and considering ethics. It prepares students for a senior thesis based on research. Said McCaffery, “It is a privilege to work with such talented students.”

McCaffery also supervises eight undergraduate student exploring links between the amylase enzyme, stress and eating, with some students writing review papers and three others leading a pilot project to test the concept using mobile phone technology. One of the students is developing the protocol to send texts to participants throughout the day to ask about their stress levels and eating behavior and collect saliva samples as part of an honors thesis in allied health sciences.

The future of health promotion at UConn

McCaffery also is advisor to graduate student Lauren Corso, a first year Ph.D. student in the health promotion program within AHS.

Corso is interested in a new field called metabolomics, which McCaffery describes as an important concept for the future of health promotion. UConn recently opened a new proteomics and metabolomics facility, and Corso will be training at the new center to study the role of metabolomics in weight and cardiovascular risk.

McCaffery is excited about potential UConn research advances that lay foundations for the treatment of obesity and diabetes. And, if her research confirms it, one of the key pieces is genetics, especially variation in the salivary amylase gene.

This research was supported by a NIH/NIDDK grant, #R21DK109225 in collaboration with colleagues at Wake Forest University, University of Maryland, College Park, George Washington University and UConn.

By Patsy Evans

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