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Single genetic defect causes early heart disease

A team of researchers from the United States and Iran has identified a genetic mutation that causes early onset coronary artery disease in members of a large Iranian family. The genetic mutation leads to heart disease by causing high blood pressure, high blood levels of "bad cholesterol" and diabetes, all risk factors for heart disease. Coronary artery disease is the leading cause of death worldwide.

"Unfortunately, most of the individuals in this family who carried the mutation died in their early fifties from coronary artery disease that resulted in heart attacks and heart failure," said the research team leader, Richard P. Lifton, a Howard Hughes Medical Institute investigator at Yale University School of Medicine. "Our studies identify a single mutation that has quite a large effect on many of the metabolic risk factors for coronary artery disease."

Lifton and his colleagues published their research article in the March 2, 2007, issue of the journal Science. Arya Mani, a cardiologist and member of Liftons laboratory at Yale, was first author of the article. The Yale group collaborated on the studies with researchers at Amir Kabir University of Technology, Azad University and The Social Welfare and Rehabilitation Sciences University, all of which are in Tehran, Iran.

The genetic defect is rare, so the discovery by itself will not provide an explanation for the more common forms of coronary artery disease, which are caused by a constellation of factors, said Lifton. However, he said, understanding the molecular nature of this single genetic defect, which is at the root of a familial form of such a complex disease, offers invaluable clues. Researchers may be able to apply that knowledge to improve understanding of what causes the bodys metabolic machinery to malfunction in the more "garden variety" forms of heart disease.

According to Lifton, physicians in Tehran had long been aware of the familys tragic struggle with early coronary artery d
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
1-Mar-2007


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