UOHI researchers have identified a stretch in the DNA sequence that increases risk of heart disease by up to 40 per cent regardless of other established risks such as cholesterol, blood pressure and diabetes. The discovery could help identify people at high future risk for heart disease, enabling early preventive therapies, including lifestyle changes and medication, to reduce their risk. This finding may also lead to a better understanding of the biological pathways that lead to heart attacks.
A study led by Dr. Ruth McPherson, Director of UOHI’s Lipid Clinic and Lipid Research Laboratory, in collaboration with Dr. Jonathan Cohen at the University of Texas Southwestern Medical School, examined the DNA of heart patients and healthy ‘controls’ from Ottawa. The participants were part of the Ottawa Heart Study in which the DNA of 1,300 patients and 1,500 healthy ‘controls’ were scanned for genetic variants. Heart Institute researchers then collaborated with scientists directing several other large-scale heart disease studies in the United States and Denmark to verify their findings.
The results, published in Science Express, showed the variant is estimated to account for approximately one-fifth of the incidence of heart attack in populations of European origin, and nearly one-third of early onset cases. The research findings point to one of the most significant genetic risk factors found to date for heart attacks and pave the way for tests to show who is at risk and for possibly new treatments.
The findings were made by two independent groups of researchers and may help scientists understand why people have heart disease even in the absence of other risk factors more commonly associated with heart disease.
The study results were based on samples from more than 23,000 people in Canada, the U.S. and Denmark. These included 2,765 in Ottawa, 10,578 Danish men and women who form the Copenhagen City Heart study, 11,478 men and women enrolled in the U.S.-based Atherosclerosis Risk in Communities (ARIC) project and the Dallas Heart Study. In all three ‘validation’ studies, this genetic variant was significantly associated with coronary heart disease.
Anna Helgadottir of Iceland-based deCODE genetics in Reykjavik and U.S. colleagues at Emory University in Atlanta, the University of Pennsylvania in Philadelphia and Duke University in Durham, North Carolina tested 17,000 people.
Both groups found the same results.
“This is an important finding for several reasons,” said Dr. McPherson. “This is a common genetic variant that has a very strong effect on heart disease risk, which isn’t related to other factors that we already know about. Heart disease is a major cause of death in western countries and the lifetime risk of developing heart disease is about one in two for men and one in three for women. If we can identify genetic factors that 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.”
The Heart Institute scientific team included Dr. McPherson, an endocri - nologist and molecular biologist, Dr. Robert Roberts, UOHI President and CEO, who is both a cardiologist and a geneticist, and Alexandre Stewart, PhD, Principal Investigator, Ruddy Canadian Cardiovascular Genetics Centre.
“Our research is uncovering the genetic predisposition to heart disease so that we might soon be able to develop individually tailored treatments,” said Dr. Roberts. “Science has excellent insight as to how to cope with environmental factors such as obesity, but genetic influence on heart disease is less clear. The Heart Institute is targeting these questions.”
The Heart Institute employs a state-of-the-art Affymetrix GeneChip®, which processes massive amounts of miniature arrays, identifies genes and allows researchers to determine patterns of genetic activity. The Ottawa Heart Study is considered to be the first genome-wide scan to search for coronary heart disease genes using an even larger number (500,000) of genetic markers and is likely to reveal still more about the genetic causes of heart disease.
In the Ottawa study, men older than 65 years and women older than 70 years who had no symptoms or history of coronary heart disease (CHD) were recruited. The patients selected for the study had severe premature CHD. People with diabetes and very high cholesterol were excluded.