Some of the most dangerous risk factors for heart disease may lie hidden, revealing no symptoms of their harmful natures until striking victims with potentially fatal heart disease or diabetes.

Researchers from the Center for Human Nutrition are leading a multinational study to identify the genetic aspects of this clustering of risk factors, called the metabolic syndrome. The metabolic syndrome, also known as the deadly quartet and syndrome x, is the concurrent appearance of high blood triglycerides, low levels of high-density lipoproteins (HDL) - the so-called good cholesterol, high blood pressure and glucose intolerance.

Twenty-five percent of middle-aged adults have it. The consequences of the metabolic syndrome are two dreaded conditions: diabetes and coronary heart disease. But in addition, patients with the metabolic syndrome also appear to be prone to developing stroke, kidney failure and, perhaps, cancer, said Dr. Scott Grundy, director of the Center for Human Nutrition at UT Southwestern and principal investigator of the study.

Genetic Epidemiology of Metabolic Syndrom (GEMS) is the largest study of its kind and will include institutions in Australia, Canada, Finland and Turkey. It is sponsored by Glaxo Wellcome.Heart disease is the No. 1 killer of Americans, while diabetes is the sixth leading cause of death by disease in the United States. UT Southwestern initiated the study after detecting a trend in pilot-project data. We noticed that a high proportion of people with high triglycerides had a first-degree relative with diabetes--about 75%, said Dr. Jonathan Cohen, UT Southwestern assistant professor of internal medicine and a scholar in the nutrition center. High triglycerides are not a contributor to diabetes, but they have some cause.

The growing obesity problem in the United States and around the world does not bode well for the incidence of the metabolic syndrome. Moderate obesity is associated with the overproduction of triglycerides, decreased HDL, elevated blood pressure and glucose intolerance, said Dr. Grundy. Obesity can bring out the metabolic syndrome in people who are genetically predisposed to it. The syndrome in turn promotes the development of coronary heart disease.

"The number of Americans with obesity is growing rapidly, which means that physicians will see more and more patients with the metabolic syndrome, diabetes and heart disease," he said. A high blood-triglyceride level appears to be the earliest clinical sign of the metabolic syndrome. This new study will recruit Caucausians with high triglycerides and their siblings--who do or do not have elevated triglyceride levels.

By studying families with a genetic predisposition, researchers hope to identify the genes and/or the location of genes associated with susceptibility to the metabolic syndrome."This is the first step in understanding the underlying pathophysiology of the metabolic syndrome," said Dr. Cohen. "The identification of culprit genes ould help us predict who will develop the metabolic syndrome and provide new targets for drug therapy."

Study participants will give a blood sample and an extensive medical history. They will receive blood-cholesterol testing, high-blood pressure testing, and blood-glucose testing. "Blood-glucose screening is significant because 50% of people who have diabetes are undiagnosed," said Dr. Cohen. "By the time they are diagnosed, they often have advanced coronary artery disease." Participants also will receive a modest cash incentive. Interested patients should contact GEMS coordinator Deborah Widmer at 214-648-5629 or by e-mail at lipids@crcdec.swmed.edu