DNA defect tied to coronary risk
Scientists using powerful new genetics-research methods have for the first time identified a snippet of DNA common to many people that dramatically increases the chances of developing heart disease.
The discovery, disclosed in two large and independent studies in North America and Europe, indicates that 75 percent of Caucasians possess a previously unknown genetic defect that puts them at elevated risk of a heart attack regardless of bad habits -- smoking, for example -- or bad health, such as hypertension or high cholesterol levels. The increased risk is most substantial for the 25 percent of Caucasians who have two copies of this defective DNA, one on each set of chromosomes.
"This is one of the most significant genetic risk factors found to date for heart attack," said Dr. Kari Stefansson, chief executive of DeCode Genetics, an Iceland-based company famous for its gene-hunting prowess.
The defect, he said in a telephone interview, "may account for one-fifth of heart attacks" among white North Americans and Europeans.
In black Americans, the defect was not associated with increased risk of heart disease, and the researchers said more study of various racial groups was needed.
Scientists involved in the studies said the findings could quickly lead to new diagnostic tests to better predict an individual's predisposition to heart disease. In the long run, the findings could lead to therapies, such as drugs, to combat heart disease at the genetic level.
Heart disease is the leading cause of death in the Western world. In the United States alone, some 1.2 million people suffer a heart attack every year and at least 452,000 die from it, according to the American Heart Association.
Human DNA is mostly the same, with less than 1 percent varying among individuals. Those differences, called gene variants, can account for such distinguishing traits as green eyes or blond hair. But certain gene variants can also translate into susceptibility to diseases.
The newly-identified genetic variant appears unrelated to other risk factors for heart attack, according to the studies, which were published online yesterday by the journal Science.
Scientists believe that they will ultimately find many genes that contribute to heart disease, just as there might be genes that protect the heart. They also stress that environmental and lifestyle factors can cause heart disease in individuals without a genetic predisposition.
The location of the gene variant stirred intense medical interest. Both studies showed that this morsel of DNA appears to be in almost the same "neighborhood" as gene variants linked to the most common form of diabetes, which were reported by scientists only last week.
At the very least, that's extraordinary coincidence. It also raises the possibility of a lethal bunching of DNA responsible for multiple ailments.
"It's a stunner," said Dr. Francis S. Collins, director of the National Human Genome Research Institute , part of the US National Institutes of Health . Collins was not involved in either heart study. "It seems like this place [possibly] carries all of that weight for two very common and very dangerous diseases."
It is unclear why gene variants associated with the two diseases might be in such close genetic proximity.
"This may suggest a causal link between these two disorders that is much deeper than previously suspected," Dr. David Altshuler, director of medical and population genetics at the Broad Institute, a Cambridge research center affiliated with Harvard and the Massachusetts Institute of Technology, wrote in an e-mail.
"It is too early to say anything with certainty, but very exciting days, to be sure," he said.
Altshuler led one of the diabetes research teams but was not involved with the hunt for the heart disease genes. Of the overall heart variant discovery, he said: "It is an extremely convincing and exciting finding, with great potential to influence our understanding of coronary artery disease."
The Canadian and Icelandic researchers compared people who had heart disease with healthy individuals, looking for common genetic variants that were far more prevalent among the heart patients. They found that an individual who possesses two copies of the newly-identified genetic variant has a 30 percent- to 40 percent-higher risk of having a heart attack than an individual of comparable age and health who does not. A person carrying a single copy of the defect has a 15 percent to 20 percent increase in risk.
Discovery of the genetic variant represents a potentially important diagnostic tool , but researchers acknowledge that genetic research is still a long way from yielding drug treatments targeted at the gene defect.
"The hope is that by discovering genetic predisposition to heart attack, we can identify people who are at greater risk for genetic reasons alone and in the long run can develop custom-tailored treatments," said Dr. Ruth McPherson, an endocrinologist at the University of Ottawa Heart Institute who led the Canadian research team.
It's been known for some time that heart disease can run in families, but previously identified "bad" genes have tended to be rare or linked to other illnesses that cause or exacerbate coronary ailments.
Big discoveries have been rolling in thick and fast in recent months, however, based on large population studies and the completion of the landmark Human Genome Project in 2003.
"Instead of vague corollaries, we're finding very robust relationships" between genes and disease, said McPherson, who spent four years studying the DNA of 23,000 heart patients and healthy "control" individuals in the United States, Canada, and Denmark.
The Reykjavik , Iceland, study scrutinized the DNA of about 17,000 US and Icelandic heart patients and healthy individuals . "The competition is getting harder, but discoveries are starting to be made at a fantastic rate," said Stefansson.
One important reason, geneticists say, is that they now understand that to identify common genetic variants, it is necessary to look at only about 500,000 of the 10 million genetic locales where human DNA differs.
"There is a real revolution going on," said Dr. Teri A. Manolio, a genetics epidemiologist with the National Human Genome Research Institute .
"We're much more able to scan the entire genome and look for variations on much vaster vistas."
Colin Nickerson can be reached at nickerson@globe.com. 