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Scientists work to identify genes that contribute to early heart attack risk

Scientists at Wake Forest University Baptist Medical Center and colleagues at four other medical centers have launched a $10 million multi-year study to identify genes that may contribute to early atherosclerosis.

"If we can identify people in their teens and early adult life who have a genetic predisposition to develop atherosclerosis, we can manage their risk factors for heart disease and stroke sooner and more aggressively," said David Herrington, M.D., M.H.S., professor of cardiology at Wake Forest and lead investigator.

Other participating centers are Cedars Sinai Medical Center, Louisiana State University (LSU) Health Sciences Center in New Orleans, the University of Texas Health Science Center at Houston and the University of Washington.

Funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, the study, known as SEA (SNPs and Extent of Atherosclerosis), will build on research from two previously funded NHLBI projects. The study will also benefit from a unique collaboration with Perlegen Sciences Inc., a company that specializes in techniques to uncover the genetic causes of diseases.

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Atherosclerosis is the development of fatty deposits in arteries that leads to blood clot formation, angina, heart attack and stroke. This process can begin in childhood and early adult life. Doctors have known that genetic factors contribute to risk for early atherosclerosis but the exact genes involved are not yet known.

"We hope the SEA study will give us new understanding about the causes of atherosclerosis, including the discovery of new genes and new pathways that could guide the development of new drug treatments that may be more effective in preventing the development of heart disease," said Herrington.

The researchers will take advantage of data from two large-scale studies: LSU Health Sciences Center’s Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study and the Multi-Ethnic Study of Atherosclerosis (MESA).

Using DNA data from the PDAY study, the scientists will work to pinpoint specific atherosclerosis genes. This autopsy study included about 3,000 young people, ages 15 to 34, who died from accidental causes, suicide and homicide. This study, which started in 1985, provided some of the best evidence that the process of atherosclerosis begins in childhood and adolescence. Using the latest technology, scientists will screen tissue samples from the study looking for genetic variants that may predispose individuals to develop early atherosclerosis.

"Perhaps the most remarkable thing about this study is the large number of genetic variants that we’re going to study," said Herrington. "Using special technology provided by Perlegen Sciences, we will examine more than 2 million different gene variations."

In part two of the study, the scientists will work to confirm their findings by determining if any genetic factors associated with early atherosclerosis in PDAY subjects also predict atherosclerosis in living participants of the $68 million MESA study. This 10-year multi-center study began in 2000 and is working to find new ways to detect heart disease before any symptoms occur.

The MESA study examined about 6,800 men and women, ages 45 to 84, who had no known heart disease. These participants were screened for atherosclerosis using non-invasive imaging tests. There are six study sites, including Wake Forest.

The researchers said it will take about five years to complete the SEA study.

Karen Richardson | EurekAlert!
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