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Two massive and independent studies have discovered a significant new risk factor for heart disease — a menacing hunk of DNA that half of all Caucasians carry.
Researchers found the heart risk linked to this genetic trait held up regardless of whether other well-known signs of susceptibility, such as high blood pressure, smoking or high cholesterol, are present.
As a result, the finding raises the prospect of a genetic test to help identify people at high risk of heart disease and measures to prevent it. It could also lead to a better understanding of the biology behind the world's No. 1 killer, since no one yet knows how this genomic quirk works.
"This is a very common genetic variant which has a very strong effect on heart disease risk that isn't related to other factors that we already know about," said Ruth McPherson, professor of medicine with the University of Ottawa Heart Institute and lead author of the report published today in the journal Science.
Researchers at the University of Ottawa Heart Institute have identified a piece in the DNA sequence that increases a person's risk for heart disease by up to 40 per cent. Pictured from left are Dr. Ruth McPherson, Dr. Robert Roberts, and Alexandre Stewart, PhD. (CNW Group/University of Ottawa Heart Institute)
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"It's important because we know that a family history of heart disease can increase the risk two-fold, and this sheds some light on that," said Dr. McPherson, whose co-authors include Jonathan Cohen from Texas Southwestern University and doctors at Copenhagen University Hospital.
Based on research involving 23,000 people in Canada, the United States and Denmark, scientists found that 50 per cent of Caucasians carried one copy of an altered stretch of chromosome 9, and as a result, their risk of developing heart disease rose by 15 to 20 per cent. A quarter of Caucasians carried two copies and faced an increased risk of as much as 40 per cent.
At the same time, in a study of 18,000 men and women in Iceland, also published today in Science, a separate research group also identified this region of chromosome 9 as one that could result in as much as a two-fold increase in heart disease risk.
Meanwhile, in a coincidence that has even top geneticists surprised at the odds, three different groups reported last week that this same region of chromosome 9 could also raise the risk of Type 2 diabetes.
Francis Collins, director of the U.S. National Human Genome Research Institute and one of the diabetes investigators, said: "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.
"I never would have guessed that we would end up coalescing, zeroing in on the same 50,000 base pairs out of three billion [chemical units that make up DNA]…"
No one knows the full function of this DNA region or how it contributes to coronary disease, which strikes one in every two men and one in every three women.
For this reason, Sonia Anand, an associate professor of medicine at McMaster University in Hamilton, said that testing people for the trait would be premature.
"The issue is what would [a test] add at this time, beyond what you can learn by asking somebody about their family history? …We don't know what to do about it. Will diet make a difference [to reducing this genetic risk]? What drug would you give?" said Dr. Anand, a co-investigator of the InterHeart project, which, among other things, is studying the DNA of 22,000 people from 52 different countries for genes linked to heart disease.
Still, Dr. Anand said the new genetic link found "seems to be a real association" and called the study "an example of how carefully this kind of work has to be done."
The priority now, she said, is for researchers to investigate how this genetic region works.
Dr. McPherson agreed that while a test is possible, "we don't want to promote this too strongly." In part, she worried that people who find out they don't carry the trait might get the wrong message and assume they're safe to smoke, or make other risky lifestyle choices.
"The risk," Dr. McPherson stressed, "is not absolute."
The research, for example, showed that while 33 per cent of people with two copies of the genetic trait had heart disease, 24 per cent of elderly people who were also carriers were healthy.
While the effects of the genetic trait are strong, Dr. McPherson said they are not as powerful as smoking, which can result in a four-fold increase in heart disease risk, or high cholesterol, which can boost the risk eight-fold.
Dr. McPherson said, however, that "if we can identify genetic factors which influence heart disease risk over and above known risk factors, we can do a better job of identifying those people who will benefit most from early intervention to reduce their risk."
Their research found that the chromosome area involved in the new heart risk houses two genes and roughly 66 different genetic alterations between them. Those genes, CDKN2A and CDKN2B, are known to be involved in cell growth and cell death. In their paper, researchers speculate the region might somehow contribute to clogging arteries.
It's possible the altered region might regulate those genes, Dr. McPherson said, or perhaps other neighbouring genes.
Dr. McPherson explained that this altered stretch of DNA has been passed down to carriers in a chunk through the generations — a heritable block known as a haplotype.
In fact, researchers cross-referenced their findings against the International Haplotype Map, the first catalogue of common genetic differences between four ethnic groups, Europeans, Han Chinese, Japanese and the Yoruba people of Nigeria.
They found that while these genetic changes were common in Europeans, some were either non-existent or rare in people of African descent.
Dr. McPherson said the mutations might be prevalent in other populations besides Caucasians, but that their work happened to involve largely Caucasian samples.
It's not the first time heart research has divided along colour lines.
In 2005, for example, the U.S. Food and Drug Administration took the unprecedented step of approving the heart drug BiDil for use in blacks. This came after research suggested it was effective only in that population. But since no one knows why this is the case, many have warned that it might not work for all blacks and that non-blacks might also benefit.
