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Gene clusters predict atherosclerosis severity, susceptibility

ine genomic techniques to address the risk for complex disorders like atherosclerosis," said cardiologist Pascal Goldschmidt, M.D., senior member of the research team and chairman of Duke's Department of Medicine.

"After seeing the results of this study, I am extremely encouraged that at some point after further research we will be able to help fulfill the promise of personalized medicine," Goldschmidt. "This would not have been possible without the collaborations across this institution, as well as the support of the National Institutes of Health."

For their experiments, the research collected more than 60 fresh aorta samples from humans whose hearts had been harvested for organ transplantation. The aorta, the body's largest artery, takes blood ejected from the heart and distributes it throughout the body via smaller arteries. The samples ranged from healthy to severely diseased.

The researchers then "mapped" not only the degree of atherosclerotic plaque development, but also the locations of the plaque within the aorta. Location of the plaque is an important indicator of disease susceptibility, the researchers said, because atherosclerosis tends to progress toward the heart.

Once the samples were mapped by defined segments, the researches then performed a DNA microarray, or gene chip, analysis of each region. Using this new technique, researchers can quickly screen more than 12,500 known genes, searching for those that are "turned on," or are expressing themselves.

In terms of severity of disease, the researchers found a cluster of 208 genes that predicted severe disease in 29 out of 31 (93.5 percent) tissues samples, and a cluster of 28 genes that predicted location of disease in 59 out of 63 samples (93.6 percent).

In general, many of the genes found within the clusters were known to researchers, although there was very little overlap between genes identified in the severity and
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Contact: Richard Merritt
Merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
28-Sep-2004


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