Gene Material Strongly Linked to Heart Disease

The same cluster raises diabetes risk, too, and a test is in the works, scientists say

WEDNESDAY, May 2, 2007 (HealthDay News) -- Two research teams have each identified genetic material strongly associated with a significantly increased risk of heart disease.

A test focused on the genetic variants, located on chromosome 9, might identify people at high risk of heart attack. About one in every four Caucasians are thought to carry the gene variants, and a test to spot those at risk could be available by the end of this year, the head of one research group said.

The discoveries are even more interesting, because the same region has recently been strongly implicated in bumping up diabetes risk.

"This is an important finding, because it was replicated in different populations around the world," added Canadian scientist Dr. Ruth McPherson, director of the Ottawa Heart Institute's lipid clinic and lipid research laboratory, who led one research effort.

The two separate reports, published in the online edition of the journal Science, do not pinpoint specific genes. Instead, they cite what are called "single nucleotide polymorphisms" (SNPs) -- slight variations in the sequence of units that make up the molecule of DNA that carries genetic information.

One report, led by scientists at deCODE genetics Inc., an Icelandic biotechnology company, cites a SNP called rs10757278. A second report, this time led by McPherson's group in Canada, cites two SNPs -- rs10757274 and rs2383206. All are clustered together in a region of chromosome 9.

Regardless of where the study participants (all white) originated -- Canada, Iceland or the United States -- the SNPs bumped up heart risk. For example, persons carrying the SNP cited in the deCODE study had about a 60 percent raised risk for heart attack compared to non-carriers, while people carrying the two SNPs in the Canadian study had a 30 percent to 40 percent increased risk of heart disease.

The SNPs are different, because the two groups used different versions of the chips that allowed them to parse the DNA unit by unit, McPherson explained. Her group used a chip made by one company, Affymetrix, while the other chip was made by Illumina.

The discovery that these SNPs can impact heart risk remains puzzling, because they do not involve specific genes, McPherson said. However, they do lie near two tumor-suppressor genes known to be associated with cell proliferation, aging and death. There might be other explanations for the association, she said.

"They may be in a region that regulates the activity of genes," McPherson said. "It is possible that the region regulates genes that are a bit further away. But the finding so far does not tell us anything about their mechanism of action."

Still, there is "a kind of excitement about such unexpected findings that could lead to genes with entirely different pathways," McPherson said.

Part of the excitement is that the genetic factors identified by the studies do not seem to be linked to known risk factors. That opens the possibility of new preventive measures aimed at whatever in the SNPs influences heart risk.

And there's another bonus: A team led by Dr. Francis Collins, director of the U.S. National Human Genome Research Institute, recently reported that the same genetic material is also highly linked to a boost in diabetes risk.

"How can one region of the genome, and it is not even containing a gene, contain risk factors for both diabetes and heart attack, when they don't seem to be heart attack on the basis of diabetes?" Collins told reporters at a special seminar on Tuesday. "I think this is a stunner. This is like the seat of the soul of the genome. It seems like this one place carries all of that weight for two very common and very dangerous diseases."

The deCODE team was similarly enthused.

"The most important story is that not only does this variant impose the risk of heart attack, but it imposes greater risk on younger people," said Dr. Kari Stefansson, a neurologist, formerly with Harvard Medical School, who is now deCODE's chief executive officer. "For men under the age of 50 and women under the age of 60, it doubles the risk of heart attack."

A test based on the finding will be available probably before the end of this year, Stefansson said. "We plan to launch it ourselves. Regulatory approval is not required."

The test would be aimed at two groups of people, he said -- those with known risk factors such as high cholesterol, high blood pressure and diabetes, and those whose physicians wanted to screen them for risk. When someone is found to carry two risk-associated SNPs, "those are the people you want to follow meticulously," with close attention to risk factors," Stefansson said.

"Ultimately, such a test could be added to the whole package that we use to assess risk," McPherson said.

More information

There's more on SNPs and their role in genetics at the Human Genome Project.

SOURCES: Ruth McPherson, director, University of Ottawa Heart Institute lipid clinic and lipid research laboratory; Kari Stefansson, M.D., chief executive officer, deCODE Genetics, Iceland; May 1, transcript, U.S. National Human Genome Project; May 3, 2007, Science Express
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