Genetic experts investigate causes of harmful metabolic disorder

December 05, 2006

Cincinnati -- University of Cincinnati (UC) researchers have received more than $1.6 million from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study genetic causes of metabolic syndrome, a disorder that can lead to cardiovascular disease and diabetes.

"Metabolic syndrome has emerged as a public health problem of epidemic proportions in Western societies like the United States," says Ranjan Deka, PhD, the UC environmental health professor who will lead the international study. "To combat this complex disease, we need to establish genetic biomarkers--but we also need to understand lifestyle patterns and make necessary changes."

Metabolic syndrome is a combination of inherited risk factors, and, according to the American Heart Association, about 25 percent of Americans have it. Untreated, it can lead to life-threatening health problems such as coronary artery disease, stroke and type 2 diabetes.

This UC-led study aims to identify and isolate the specific genes associated with metabolic syndrome so that scientists can identify at-risk populations.

"Metabolic syndrome is a complex disease that can't be attributed to just one cause," explains Deka. "Genes don't act alone. They work in concert with the environment, so exposures as well as lifestyle choices and diet can contribute to it."

Deka believes that genetic dispositions may be coming together with changed lifestyle--one of unhealthy food intake, little exercise and an overall sedentary lifestyle --to cause metabolic syndrome.

Primary risk factors for the condition include central obesity (around and in the abdomen), high blood pressure, glucose intolerance and blood-fat disorders that promote plaque buildup in the artery walls.

Deka and his team will attempt to establish a genetic basis for metabolic syndrome by identifying chromosomal regions associated with it. They will collect data from a genetically isolated population of about 80 large families living in the islands of Croatia.

Because these islanders are a traditionally isolated society, Deka says, the people have a very homogeneous genome. This eliminates many of the confounding effects of a diverse population and is more conducive to research designed to isolate specific genetic causes of a disease.

Croatians also have many risk factors for metabolic syndrome--including obesity and high blood pressure--that cannot be explained by poor diet or lifestyle choices.

"This is unusual," explains Deka, "because this population eats a traditional Mediterranean diet, which is thought to be very healthful. We believe these risk factors may be primarily linked to genetics, not lifestyle and environmental exposures."

Deka and his team will collect blood samples, environmental data (such as diet and lifestyle), family medical history and other demographic information from about 1,200 individuals from the Croatian islands. They will perform DNA analysis on each person to identify genetic markers that may be linked to metabolic disease.

"By understanding what genetic mutations exist and where they are within the body's genetic make-up, we can identify correlations between genetic abnormalities and specific diseases," Deka says. "When we can do that, we'll have a better understanding of how to treat the underlying causes of complex diseases."
-end-
Study collaborators include UC's Ranajit Chakraborty, PhD and Pavao Rudan, PhD, of the Institute for Anthropological Research in Croatia as well as researchers from the University of Pittsburgh and Cincinnati Children's Hospital Medical Center. Deka and his team will travel to Croatia in March 2007 to conduct initial field work.

University of Cincinnati

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