WEDNESDAY, Dec. 3, 2003 (HealthDayNews) -- Now that scientists say they've identified the first gene mutation responsible for heart attacks, doctors have to decide how best to use this information.
Although the mutation has only been isolated in one family with roots in Iowa, the finding may shed light on the genetic pathways involved in early coronary artery disease and heart attacks, researchers say.
It also offers a new risk factor to consider, and a way to decide who needs to be extra vigilant about heart health.
"Until we have gene therapy, we are left with getting more aggressive with risk factors, isolating who's at higher risk and trying to change the course of the disease," says Dr. Daniel Fisher, a clinical assistant professor of medicine at New York University School of Medicine. "This is just something else that we're going to say let's get more aggressive."
A study on the findings was published in the Nov. 29 issue of Science.
The role of genetics in coronary disease is difficult to untangle because it's a so-called late-onset disease, experts say.
"By the time you find somebody, the parents have already died and the children are too young to have had the disease, which is critical to being able to do the work," says Dr. Eric J. Topol, senior author of the new study and chairman of the department of cardiovascular medicine at the Cleveland Clinic.
Topol got lucky when a heart attack patient arrived one day in his clinic with heart failure. During that first consultation, the man happened to mention he had 10 siblings, nine of whom had had heart attacks. "That was a pretty strong signal" that there was a genetic link, Topol says.
Despite the high incidence of heart attacks in the family, none of its members had high cholesterol levels, which are extremely common in heart attack victims. "Most people who have a heart attack have abnormal cholesterol, so it had to be something more penetrating and important than cholesterol to explain the disease," Topol says.
"It" turned out to be cracks in an arterial wall.
When the researchers did a genetic analysis of 13 family members (nine of whom had had a heart attack), they identified a region on chromosome 15 that includes a gene thought to be involved in blood vessel development. They hit pay dirt when they discovered that family members with heart disease all carried a mutated version of the gene MEF2A. Those without the disease didn't have the mutation.
The mutated version of the gene MEF2A "at birth sets up an artery wall that is not intact and then predisposes the person to a heart attack," Topol explains.
"It's a 100 percent risk, unless they get hit by a car," Topol says. "It's a pre-committed path to a heart attack." The heart attack usually occurs in men 45 and over and in women 50 and over.
All the family members who suffered a heart attack also had at least one other risk factor for an attack, such as obesity or smoking, so there seems to have been some contribution from environmental factors. What researchers don't yet know is how important those environment factors are. Could altering them stave off a heart attack in those with the genetic mutation?
"We know there's a defect in the artery wall, and if someone doesn't have the risk factors, they may still get this disease but it should be deferred substantially" by pursuing a healthy lifestyle, Topol says. "It is pretty unlikely that they could ward it off completely."
Since that first family member arrived in Topol's examining room, some 250 family members have been studied and given their genetic information. And the number keeps growing.
Having this information "changes everything," Topol says. "Now to be told you do or don't have this gene is a whole different story. It's much more definitive. If you do have this gene, many of them have a long way to go to turn around that risk. And in the ones who don't have the gene, it's a tremendous amount of mental relief."
People with the gene say they'll stop smoking and lose weight, and Topol intends to follow them to see if they really do.
In a matter of days, the parents of a 17-month-old girl will know if she has the mutation or not. This could affect the way her parents bring her up.
"Hopefully this [heart attack risk] can be changed at the earliest age," Topol says. "This is a disease that takes at least 20 to 30 years to incubate, so if you can start early, it's remarkable how much you can do."