Scientists at The Cleveland Clinic have identified the first gene confirmed as a cause of coronary heart disease in humans. Results of this groundbreaking research will appear in the Nov. 28 issue of Science.

The gene, MEF2A, was discovered by methodically studying the genetic makeup of 21 members of an Iowa family plagued for generations by incidents of coronary artery disease and heart attack. (Research with the family has continued beyond preparation of the Science article. Of the more than 50 family members who have provided DNA, the genomes of 26 family members now have been analyzed.)

 “What we discovered is a deletion mutation,” said Eric J. Topol, M.D., chairman of the Department of Cardiovascular Medicine at The Cleveland Clinic. “The elements missing from this gene represent 21 base pairs of nucleotides and seven amino acids. This deletion affects coronary artery walls, making them less able to protect themselves from plaque buildup and heart disease.”

Dr. Topol discusses the study’s significance.

Dr. Topol, who also serves as the Clinic’s provost and chief academic officer, said it is unlikely that many other families will be found with the exact same genetic mutation. Instead, researchers will seek to pinpoint smaller mutations involving the same gene that may contribute less dramatically to the development of heart disease.

“People with this exact MEF2A mutation have essentially a 100-percent chance of having a heart attack or developing coronary artery disease,” Dr. Topol said. “For them, it’s not a matter of ‘if,’ it is a matter of ‘when.’ For that reason, we think this specific mutation will prove to be rare. Most genes that will be discovered to induce heart attack will be more common and not carry as high a risk.”

No matter what the future of heart disease research holds, Dr. Topol said, one message remains clear: “Lifestyle choices are vitally important in the fight against heart disease. For people with this deletion mutation, their battle is to identify and control lifestyle factors — weight, blood pressure, diet — to delay the onset of heart disease as long as possible. For people without a genetic predisposition, they must make it their responsibility to take care of themselves to prevent heart disease from developing.”

Dr. Topol discusses breakthrough findings 

Every patient in the Iowa family who experienced a heart attack had at least one coronary risk factor. As Cleveland Clinic scientists looked for the genetic link, researchers in the laboratory of Qing Wang, Ph.D., scanned the complete genomes of all participating members of the family.