'Heart Attack Gene' Discovered at Cleveland Clinic Exists in 1-2% of U.S. Heart Attack, Coronary Artery Disease

October 20, 2004

New Clinic Research Advances Efforts to Understand Genetics of Heart Disease

In November 2003, Cleveland Clinic researchers announced the discovery of the first gene confirmed as a cause of coronary heart disease in humans. Less than a year later, their studies indicate this "heart attack gene" is more prevalent among Americans than expected.

According to their findings, as many as 1 percent to 2 percent of all U.S. heart attack and coronary artery disease patients may carry mutations of the MEF2A gene. Cleveland Clinic researchers discovered this gene by methodically studying the genetic makeup of 21 members of an Iowa family plagued for generations by clogged arteries and heart attacks.

When researchers initially discovered an MEF2A deletion mutation in the Iowa family, they acknowledged it was unlikely that the exact genetic mutation would be found in other people. Instead, they began to search for smaller mutations involving the same gene, and they found just that.

The latest mutation involves three novel mutations in exon 7, rather than exon 11 as in the original MEF2A mutation. The new mutations also involve one base pair point change, instead of a 21 base pair deletion. The full study is being posted online today in the journal Human Molecular Genetics.

"This is another exciting and vital piece in the heart-disease puzzle," said Eric J. Topol, M.D., chairman of the Department of Cardiovascular Medicine at The Cleveland Clinic. "This study indicates that coronary artery disease and heart attack can result from a spectrum of MEF2A mutations. This work along with that of other groups will quickly solve the genetic bar code for coronary disease, greatly enhancing our efforts to prevent it or make an early diagnosis."

Dr. Topol, who also serves as the Clinic's provost and chief academic officer, said the study indicates that a significant number