The devastating heart condition left main coronary artery disease is the worst form of heart disease and develops silently. Victims often experience no symptoms before sudden death. But new National Institutes of Health-funded genetic research led by scientists at the Miller School and Duke University could result in a simple blood test to detect the abnormality in those most at risk.

“Now that we have discovered a genetic link to the gravest heart disease in the world, we may be able to target more specifically patients who truly need expensive and extensive testing,” says Miller School Dean Pascal J. Goldschmidt, M.D., one of the authors of the study published in the Annals of Human Genetics. “A simple blood test for the genetic marker could be enough to identify individuals who are more susceptible to developing the condition.”

Researchers have long known that coronary artery disease has a strong genetic component, which is why family history is a risk factor. Previous studies by the same research group identified a large region of chromosome 3 as containing genes important to developing coronary artery disease. This time around, a portion of that group—led by Goldschmidt and Jeffery M. Vance, M.D., Ph.D., professor and chairman of the Dr. John T. Macdonald Foundation Department of Human Genetics, along with first author Liyong Wang, Ph.D., from the Miami Institute for Human Genomics—identified the limbic system-associated membrane protein (LSAMP) as a key gene for left main disease.

The gene had never before been linked to coronary artery disease. But in the current association study of individuals with left main disease, the researchers saw significant evidence of an association with this gene, which was also confirmed when families with at least two siblings diagnosed with early-onset coronary artery disease were studied. “Through fine mapping we were able to identify a specific area of the gene, known as the risk haplotype, that was highly associated with left main coronary artery disease and accounted for a substantial fraction of the risk for the disease in our population of patients,” says Goldschmidt.

The researchers also found evidence while studying gene expression patterns in human aortas that LSAMP is related to the formation of atherosclerotic plaques in arteries, which is a primary cause of heart disease such as left main disease.

David Seo, M.D., associate professor of medicine, and Margaret Pericak-Vance, Ph.D., director of the Miami Institute for Human Genomics and the Dr. John T. Macdonald Foundation Professor of Human Genomics, were also authors on the paper.