Diabetic gene linked to heart disease

Heart disease is the most frequent, costly and severe complication of diabetes, affecting more than 70 percent of diabetic patients. There are geographic and ethnic differences in the risk of diabetic heart disease that cannot be fully explained by differences in conventional heart disease risk factors. Using a simple blood test, researchers at the Technion-Israel Institute of Technology have identified a gene that determines which diabetes patients are at greater risk for developing heart disease. Unlike other recent breakthroughs, such as the test for C-reactive protein, the test for this gene needs to be administered only once in a patient’s lifetime.

There are two forms of this predictive gene and they are present in approximately equal frequencies in the general population and in diabetics. Diabetics with one type of the gene have a five-fold greater risk of developing heart disease than those with the other form of the gene.

“If we can accurately determine which people with diabetes are at greatest risk for heart disease with a genetic test, there is no telling how many lives we could save with early intervention techniques,” said Dr. Andrew P. Levy of the Technion Faculty of Medicine, who headed the research which was published in the December 4th issue of The Journal of the American College of Cardiology.

Dr. Eugene Braunwald, Professor of Medicine at Harvard Medical School and Chief Academic Officer at Partners HealthCare System agreed. “The demonstration in this paper that a straightforward determination of haptoglobin phenotypes can identify patients with diabetes with increased likelihood of cardiovascular disease should allow early and intensive preventive measures in such patients,” he said.

Dr. Levy and his colleagues examined the genetic makeup of individuals in a sample from the Strong Heart Study, a population-based longitudinal study of heart disease in Native Americans, a group previously thought to be resistant to developing heart disease but are now suffering from the disease in large numbers. The relative genetic homogeneity of this population, along with the high prevalence of diabetes~ makes it an ideal group to study.

The sample group included 206 individuals with heart disease and 206 control cases aged 45-74. Using stored blood samples, the researchers looked at haptoglobin, a blood protein found in three different forms: 2-2, 1-1 and 2-1. Individuals with the 2-2 form were five times more likely to have heart disease than those with the 1-1 form. An intermediate risk was associated with those with the 2-1 form.

“This is an entirely novel and new idea that will certainly attract attention from many clinical investigators and scientists worldwide,” said Dr. Myron L. Weisfeldt, Director, Department of Medicine at The Johns Hopkins Medical Institutions.

The ability of this genetic test to predict the risk of heart disease in diabetic patients regardless of ethnicity is strengthened by recently reported findings by Dr. Levy and colleagues from Germany. In that study, presented at the American Heart Association meetings in Chicago on November 19th, 935 patients with diabetes were followed after angioplasty. Individuals with the benign form of the gene were dramatically protected from suffering a heart attack or needing repeat angioplasty.

The current study also builds on previous work by Dr. Levy which reported on the association of the haptoglobin gene and other complications of diabetes such as kidney and eye damage. Articles detailing these findings were published in the New England Journal of Medicine and the Journal of the American Medical Association in September 2000. HaptoGuard, Inc., a company utilizing the technology developed by Dr. Levy’s research, hopes to build on these findings to improve management of the disease.

The Technion-Israel Institute of Technology is Israel’s leading scientific and technological center for applied research and education. It commands a worldwide reputation for its pioneering work in computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel’s high-tech companies are alumni.

Based in New York City, the American Technion Society is the leading American organization supporting higher education in Israel, with more than 20,000 supporters and 17 offices around the country.

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