Researchers have used a new gene-hunting technique to pinpoint a novel genetic variant that raises some people's odds of having a heart attack. The results, reported online today in Science, suggest a possible new contributor to heart disease and could lead to a genetic test to pinpoint people who are susceptible.
Over the past decade, many genes have been reported to increase the risk of heart disease, but few of these findings have held up in subsequent studies. In the current work, researchers applied a new approach called genome-wide association, which utilizes a set of markers spanning the entire genome, to compare the DNA of heart disease patients with that of healthy people (ScienceNOW, 26 April). In one study, researchers at deCODE Genetics Inc., in Reykjavik, Iceland, used 300,000 genetic markers to scan the DNA of 1607 Icelanders who had had heart attacks, along with DNA from 6728 healthy controls. They found a genetic variant on chromosome 9 that was much more common in people who had suffered a heart attack. They and U.S. collaborators then confirmed the association in another Iceland sample and three U.S. groups totaling nearly 4600 cases and 12,800 controls.
A separate team found the same genetic clue. Researchers led by Ruth McPherson of the University of Ottawa Heart Institute in Canada and Jonathan Cohen of the University of Texas Southwestern Medical Center in Dallas examined about 300 heart disease patients and 300 controls using 100,000 markers. The results, which point to the same gene on chromosome 9 fingered by deCODE, held up in five more groups of people in the U.S. and Denmark. Given that two separate teams found evidence for the same variant in a large number of sick people, "one can be absolutely confident that this risk allele is real," says McPherson.
The results could eventually help doctors predict which individuals are prone to heart problems. Up to one-quarter of white Europeans have two copies of the genetic variant pinpointed by the two teams. Based on the new findings, these people are at 50% higher risk for heart attack than those with no copies, and they face up to a 40% greater risk of cardiovascular disease. The increase is even higher--more than 80%--for early-onset heart attack, which strikes women before the age of 60 and men before 50, the deCODE team reports. Kári Stefánsson, CEO of deCODE, suggests it might be useful to screen young people from families with a history of heart attack for this variant so they can take extra precautions, such eating a healthy diet. McPherson is more cautious. She says first researchers should look for more variants that in combination could raise the risk higher and make the test more useful.
The genetic variant does not seem to affect blood pressure, cholesterol, or other known risk factors for heart disease, suggesting it works through some new mechanism, McPherson's team reports. Its position between genes suggests that it might regulate the production of one of these gene's protein products in a way that promotes atherosclerosis. A variant in the same location was reported last week to play a role in diabetes (ScienceNOW, 26 April). "This is a stunner," says Francis Collins, director of the National Human Genome Research Institute in Bethesda, Maryland, and a co-author of one of last week's diabetes papers, because it suggests the same gene could play a role in both diseases.