Seniors and suspects

A group of 3,000 Ottawa seniors is helping track down the complex causes of heart disease.

by Harold Eastman

How would you describe Dr. Ruth McPherson’s research? Consider a somewhat simplistic but at least entertaining analogy. Detectives are looking for a gang of thieves that has robbed a bank in a very large city. Finding the bad guys is going to be like finding a needle in an urban haystack.

The cops, however, have two advantages. First, they know from previous experience which neighbourhoods tend to harbour the city’s criminals. Second, there are lots of them—enough cops to interview every resident in all those neighbourhoods, listen in on every phone line, watch the tapes from every security camera and analyze and follow up on each of the countless leads these sources produce.

It might be a civil liberties nightmare, but our fictional cops have a good chance of catching their man.

Dr. McPherson, a researcher and physician at the University of Ottawa Heart Institute, is engaged in a search that’s similarly daunting. However, working with a cohort of Ottawa seniors and a lot of powerful technology, she’s on her way to getting some, well, arresting results.

McPherson and her colleagues are conducting a massive study of genetic risk factors for heart disease. The scale of scientific detective work involved is awe-inspiring. The long DNA molecules in each of our cells comprise 3 billion “base pairs,” the rungs of chemical connectors that make up DNA’s famous twisting ladder. Small variations in how these base pairs are connected and arranged account for about 50 percent of our susceptibility or resistance to heart disease. That makes for a lot of potential variations. Like the imaginary detectives in our analogy, however, the Ottawa researchers have a couple of things going for them. Only certain sections of our DNA contain relatively common variations—about 7 million base pairs out of the total 3 billion, significantly narrowing the number of “neighbourhoods” to be searched. And while the number of scientists is relatively low, the researchers have access to unprecedented technology that does a lot of the investigative legwork for them.

For these genetic detectives, the scientific equivalent of the citywide dragnet is the “genome-wide association study.” McPherson and her team are taking DNA samples from about 4,000 patients suffering from heart disease and from about 3,000 healthy individuals. The samples are fed into very sophisticated gene analysis machines at the Heart Institute. One of them, the Affymetrix Gene Titan, is the first operating unit of its kind in the world. The technology isolates from each sample the DNA that conforms to the “neighbourhoods” the scientists want to search and then determines which of the common genetic variants are present in the sample.

Next, the researchers use very powerful software and hardware to crunch the vast amount of information the machines produce—like detectives sifting through millions of leads— and identify which variants or sets of variants are significantly linked to the patient group or the healthy group. These variants are obviously the prime suspects in terms of genetic causes for heart disease.

The healthy “control” group consists entirely of individuals over 65.Why? Because if they’ve lived this long and haven’t developed heart disease, they’re unlikely to carry major genetic risk factors that can cause it. Another advantage: the researchers can factor in life-long environmental factors, like body weight, levels of alcohol consumption and physical activity, and include them in the study alongside the genetic information. “We think our data set will be large enough for us to actually look at what people are very interested in now: gene– environment interaction,” says McPherson.

Exercise may be a powerful counterweight to risk factors for heart disease. “When we look at this cohort of healthy elderly,” she continues, “the most interesting group comprises more than 200 subjects over the age of 85.And the question is, why are they so well?” McPherson is particularly interested in the fact that almost 90 percent of the subjects 85 or over engage in some kind of physical activity for at least 30 minutes each day.

It’s going to be some time before McPherson can start releasing her findings. But she expects that her research, and parallel studies elsewhere, will begin to have an impact in a surprisingly short period of time.

“I anticipate that within two or three years we’ll have a fairly robust collection of simple genetic markers. That would make it possible to genotype people and provide further insight into their risk for cardiovascular disease.” Working with that information, physicians and patients could devise lifestyle or pharmacological strategies to combat any added risk. Further in the future, the research might also lead to new drugs that suppress the effects of harmful genetic variants.

In the meantime Dr. McPherson’s detective work continues. And with the help of heavy hardware and healthy seniors, she’s tracking down and rounding up a growing list of suspects. 

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