A treasure hunt for genes has found a genetic mutation that significantly increases the risk of developing heart disease and the chance of a heart attack.
Two large groups of researchers from around the world who conducted complicated genetic analyses on 40,000 people came to the same conclusion — a stretch of DNA called 9q21 carried certain mutations in people with heart disease. The researchers found that the mutation — which is close to a stretch of DNA linked to diabetes — nearly doubles the risk for heart attack before age 60.
The discovery is particularly important because at least one in five Caucasians are born with the variation in the DNA that increases heart attack risk.
The research may help explain why from the time of birth a big part of a person's lifetime risk for heart attack is already determined in the DNA. People with the variations can develop heart disease even if they do not have clear risk factors such as smoking, high cholesterol or high blood pressure.
The findings could lead to a test to predict the risk of heart disease, the biggest cause of death across the globe.
“I think this is a stunner,” Dr. Francis Collins, director of the National Human Genome Research Institute, told reporters. “It seems like this one place carries all of that weight for two very common and very dangerous diseases.”
Both teams used a new method of combing the genome for disease genes called a genome-wide association study, which was not possible until the full human genome was published in 2003. Now scientists can map the DNA of people with a disease, compare them to this template genome or to people without a disease, and find what is different.
Dr. Ruth McPherson of the University of Ottawa Heart Institute and colleagues scanned blood samples from 23,000 people.
Anna Helgadottir of Iceland-based deCODE Genetics Inc. in Reykjavik and U.S. colleagues at Emory University in Atlanta, the University of Pennsylvania and Duke University in North Carolina tested 17,000 people.
"This is the single most important discovery made to date about a new finding of what genetic variations can lead to heart attack," said cardiologist Dr. Christopher Granger of the Duke University Medical Center, Durham, N.C.
The deCODE team found that about 21 percent of the people they tested had mutations in both copies of this DNA stretch, giving them a 64 percent higher risk of a heart attack than people who carried no copies of the mutation.
McPherson’s team said 20 to 25 percent of Caucasians they tested carrying two mutated copies of 9q21 and had a 30 to 40 percent higher risk of coronary heart disease than people without the mutation. Half the people had one copy and they had a 15 percent to 20 percent higher risk of heart disease.
Africans did not appear to carry the mutations, and in African-Americans, the mutations were not associated with heart disease risk, McPherson’s team wrote.
The region is not associated with inherited tendencies to have high cholesterol or high blood pressure.
But 9q21 is found near two genes called CDKN2A and CDKN2B, which four international teams of researchers last week reported they had identified in their own genome-wide association study looking for diabetes.
Collins said the coincidence was astonishing.
“We are in the same place in the genome. Here is CDKN2B and 2A, their signal, exactly in the same place as where we found an association for type-2 diabetes,” Collins said.
While diabetes raises the risk of heart disease, the heart disease researchers made sure that the patients they scanned did not have diabetes. Collins said researchers will now have to look for a mechanism that explains why a single stretch of DNA could cause both conditions.