New research uncovers fresh evidence linking genes to heart disease

Ottawa, ON – Researchers at the University of Ottawa Heart Institute (UOHI) have identified a piece of the DNA sequence that boosts a person’s susceptibility to heart disease by up to 40% regardless of other established risks such as cholesterol, blood pressure and diabetes.

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 May 3 in Science Express (Vol.316, Issue 5825, May 4, 2007), showed that a region on chromosome 9 was strongly linked to premature heart disease. Individuals carrying the genetic variant (about 25% of the population) had a 30 to 40% higher risk of heart disease than those individuals who do not carry this genetic variant. This increased risk was not related to effects on known heart disease risk factors such as cholesterol, blood pressure, diabetes or smoking.

The study results were based on samples from more than 23,000 people in Canada, the US 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 US-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.

“This is an important finding for several reasons,” said Dr McPherson. “This is a 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,” she adds. “To put this into perspective – of the groups studied in Ottawa, about 33% of people with early onset heart disease had this genetic variant versus 24% of healthy elderly people.”

The Heart Institute scientific team included Dr McPherson, an endocrinologist 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.

The Heart Institute employs a state-of-the-art Affymetrix GeneChip(R), 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 CHD 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.