Genetic patterns double heart risk

Large studies link variants to coronary disease and attacks

May 04, 2007|By Dennis O'Brien | Dennis O'Brien,Sun reporter

Researchers have identified genetic patterns that double the chance of having a heart attack and drastically increase the likelihood of suffering from heart disease, the leading cause of death in the United States.

The findings could lead to screening tests that would help people take early steps to prevent heart problems, to new therapies and to greater understanding of heart disease's biological roots, experts say.

In one of two studies reported yesterday in the journal Science, researchers who compared DNA of 17,000 heart patients and healthy volunteers in Europe, the United States and Iceland found that someone carrying a set of genetic variants on Chromosome 9p21 is twice as likely to suffer an early heart attack. For women, that's before the age of 60, and for men, 50.

"What we've found is a very significant risk factor for the most common cause of death in our society," said Kari Stefansson, the study's senior author, whose Icelandic company plans to develop a test kit to detect the sequence.

In the second study, researchers using DNA from 23,000 heart patients and healthy volunteers in Canada, Denmark and Texas found a genetic sequence on the same chromosome that increases the risk of heart disease by up to 40 percent. About one in four people carry the sequence, the researchers say.

"There's going to be a huge storm of interest here, in the next few days, as people try to figure out what is happening," said Dr. Francis Collins, head of the National Human Genome Research Institute in Washington. He noted that the heart risk variants lie close to genetic sequences that were linked to adult onset diabetes in reports published just last week.

"I think this is a stunner," he said.

Heart disease is the nation's No. 1 killer, accounting for 654,092 deaths in 2004, according to the Centers for Disease Control and Prevention. Cancer was second, causing 550,270 deaths that year; strokes killed 150,147.

The results of both studies were confined to genetic patterns found among Caucasians of European descent. The implications for other groups, including African-Americans, remain unclear.

Both papers are "very convincing" because of the large number of patients and healthy volunteers whose DNA was studied, said Dr. David Valle, director of the Institute of Genetic Medicine at the Johns Hopkins School of Medicine, who was not involved in the studies. He is researching the genetic underpinnings of neuropsychiatric diseases such as bipolar disorder.

"Together, they make a stronger story than either would by themselves," he said of the studies. "It's expensive work and it's time-consuming work, but what these papers show is it pays off."

The genetic sequences identified as coronary risk factors exist regardless of whether someone takes care of himself or smokes, overeats and refuses to exercise, the researchers say. But health experts say there is no doubt that in the general population, diet, exercise and smoking still play a major role in determining whether someone develops heart disease.

"It could be that regardless of the genetics, smoking just makes things worse," Valle said.

Alexander Pertsemlidis, a co-author of the heart disease study and a computational biologist at the University of Texas Southwestern Medical Center in Dallas, said there is no reason for testing to detect the gene patterns, in part because too little is known about how the genetic variant affects heart disease. "At the moment we're still searching for answers," he said.

In addition, he said, people concerned about heart disease are better off taking standard protective measures to ensure heart health, such as watching their diet, getting physical check-ups and exercising.

Stefansson, however, said he hopes to have a genetic test available by the end of the year so patients can give a blood sample at a doctor's office and have it sent to a company lab in Iceland. He also hopes to have a diagnostic kit available, for use by medical labs around the world, within about two years.

Costs for the tests have yet to be decided. But if the test shows that a patient is at high risk for a heart attack, that person would be better informed and more likely to take extra precautions - under a doctor's care.

Such precautions could include taking medications such as statins to lower cholesterol or having a CAT scan to check the health of coronary arteries.

"There are a number of things that can be done these days for heart attack prevention," he said.

DeCode, the company Stefansson runs, is in U.S. clinical trials of a drug designed to prevent heart attacks by reducing leukotriene B4, a pro-inflammatory molecule believed to increase heart attack risk, Stefansson said.

Asked whether the study results could be construed as a tool for promoting such heart medications, Stefansson said he found the question insulting. The study results have to be reproducible and hold up to the scrutiny of peer reviews, he said.

"If we would in any way manipulate the results, we would be punished by the marketplace more than anyone could ever be punished in academia," he said.

The hunt for disease genes has been largely made possible by the sequencing of the human genome, which was completed in 2003.

These studies are expected to soon be followed by others in which researchers using new technologies compare DNA from large groups of patients who have diseases with samples from large populations of healthy volunteers, a method known as genome wide association studies.

Seven new genes linked to adult onset diabetes were identified by DeCode researchers and other scientists using the same method last week.

"We're entering a new phase of lots of exciting discoveries," Valle said.

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