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The Unexpected Way Genes Can Double Heart Disease Risk

It’s common to think of cancer as a disease driven by the buildup of mutations in the DNA of cells. Everything from pollutants to cigarettes to exposure to everyday chemicals can alter genes, and continued exposure over a lifetime can lead to a critical mass of mutations.

Heart Disease Risk

Now, researchers say the same process may be at work in heart disease. In a paper published in the New England Journal of Medicine, Dr. Sekar Kathiresan, from the Broad Institute of Harvard and MIT, and Dr. Benjamin Ebert from Brigham and Women’s Hospital and their colleagues found a gene that builds up mutations over a lifetime and can double the risk of heart events.

While there are genes associated with greater heart disease risk, most of them are inherited. The new mutations linked to heart problems are among the first to be acquired, or picked up over a lifetime. The mutations develop among a group of blood cells known as stem cells, which divide throughout a person’s lifetime to replenish the supply of blood cells. The genetic changes the researchers found are also linked to a higher risk of developing blood cancer, but they seem to have a stronger effect on heart disease than cancer.

“This is a totally different type of risk factor than hypertension or hypercholestserolemia [high blood cholesterol] or smoking,” says Kathiresan. “And since it’s a totally different risk factor that works through a different mechanism, it may lead to new treatment opportunities very different from the ones we have for heart disease at present.”

Kathiresan and his team actually found the gene several years ago when they linked it to a 10-fold higher risk of developing blood cancers. Although the mutations increased cancer risk, the cancers were still relatively rare, but people who had them had a 40% higher risk of dying of other causes. Among those was heart disease. In the new paper, the researches looked at four different populations of nearly 8,000 people who had their genomes sequenced. Even among younger people, those with the mutations—called clonal hematopoiesis of indeterminate potential, or CHIP—showed a higher rate of heart disease.

“We were fully expecting not to find anything here,” says Kathiresan. “But the odds of having an early heart attack are four-fold higher among younger people with CHIP mutations.”

There’s still a lot to learn. As exciting as the findings are, it’s still too early to add CHIP testing to routine blood screening to identify people at higher risk of having heart problems. And because CHIP contributes to heart disease in a new way, it’s possible that the mechanisms to control CHIP-related heart events have nothing to do with cholesterol, exercise and blood pressure. “The mouse work suggests that the path to heart disease is something different from what we have been working on so far,” says Kathiresan.

More work needs to be done to determine if there are ways to counteract the effect of the mutation on plaques or control the rate at which the mutations build up in these cells. “Currently there isn’t a drug that’s safe enough or efficacious enough to treat people with,” says Ebert. “But it’s a very active area of research to identify interventions that can decrease the size of the mutated cell population or potentially eliminate them.”

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