BehindTheMedspeak: Heart attack gene identified

Eric Topol and his colleagues at the Cleveland Clinic report in a study published yesterday in Human Molecular Genetics that many more people may be genetically hard-wired to have heart attacks than previously thought.

Their new data suggest that a mutation in the gene called MEF2A may be present in 1%-2% of the general population.

For comparison, only 1% of those with a family history of breast cancer have the breast cancer gene BRCA 1.

The "heart attack gene" may be present in 1%-2% of the general population, potentially putting hundreds of thousands or even millions of individuals at risk.

Here's Sarah Treffinger's story, from today's Cleveland Plain Dealer.
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Heart attack gene also hits arteries

Cleveland Clinic researchers identify three new harmful mutations

Less than a year after Cleveland Clinic researchers identified a gene that causes heart attacks, a new study shows it's possible that hundreds of thousands of people with coronary artery disease are affected by it.

The study, led by investigators Dr. Eric Topol and Qing Wang, has uncovered three new mutations in the MEF2A gene, which makes a protein important for artery wall development.

MEF2A is a regulatory gene that controls other genes responsible for proper development of the endothelium, the barrier between blood and vessels, said Wang, director of the Clinic's Center for Cardiovascular Genetics.

If the endothelium is not properly formed, it becomes susceptible to inflammation.

"It appears that it is one of the key genes for causing heart disease," said Topol, chairman of the Clinic's department of cardiovascular medicine.

Coronary artery disease is the No. 1 killer of both men and women in the United States, killing about 500,000 each year, according to the National Institutes of Health.

Eric Olson, a professor and chairman of the Department of Molecular Biology at the University of Texas Southwestern Medical Center at Dallas, said, "It is possible to screen individuals for mutations in this gene that increase the risk" for coronary artery disease and heart attack.

"Given the vast amount of information on MEF2A," he said in an e-mail, "it may also be possible to develop novel therapies for correction of MEF2A deficiency."

Last November, Topol, Wang and others published a paper about a "deletion mutation" in MEF2A, which they found by studying an Iowa family plagued by coronary artery disease.

The gene was missing 21 base pairs of nucleotides, the building blocks of DNA.

Researchers found the mutation in every family member with coronary artery disease, but not in their relatives - or in 119 other, unrelated individuals - who had no evidence of heart disease.

At the time, Topol said it was unlikely that they would find the exact genetic mutation in many other families, but he believed the discovery would allow researchers to pinpoint other, more common mutations involving the same or related genes.

That's just what happened in the latest study, posted Wednesday on the Web site of the journal Human Molecular Genetics.

The study included 207 coronary artery disease patients and a control group of 191 people.

Researchers detected the three mutations in four of the patients, but none in the control group.

The results suggest that as many as 1.93 percent of people with coronary artery disease may carry a MEF2A mutation.

But the authors cautioned that is a "preliminary" estimate.

They noted the sample size was small and the patient group was limited to men 55 or younger and women 60 or younger at the disease's onset.

That group included individuals with a history of such risk factors as diabetes, hypertension and smoking.

They also explained that carriers of the first mutation discovered last year appear to have a more severe form of coronary artery disease than those with the newly identified mutations.

The team concluded that genetic testing for MEF2A mutations may prove useful in diagnosing patients at increased risk of coronary artery disease.

"If such patients can be identified, aggressive lifestyle improvement and pharmacologic strategies may be implemented early to offset the risk," they wrote.

Topol talked about testing options during this week's Medical Innovation Summit at the Clinic.

He told reporters that he and others hope to establish a "gene panel" that would screen for a variety of genes, including MEF2A mutations and ApoE4, a cholesterol-transporting gene.

They're still working out details, but Topol said the test should be made available for patients seeking a genetic assessment by the end of this year or in early 2005.