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Gene Mutations That Lower Heart Risks May Spur New Drugs

Scientists have identified gene mutations that reduce levels of fatty triglycerides in some people and cut their heart attack risks, potentially paving the way for new types of drugs.

For years, drugmakers focused on adjusting cholesterol levels to help people hold off heart problems. Now, a new pharmaceutical strategy may be forming based on two studies reported in the New England Journal of Medicine. The research identified mutations in the APOC3 gene that decreased heart disease risk in some people by about 40 percent.

Triglycerides are a form of fat created from excess calories the body doesn’t immediately use after eating. They gather in the bloodstream as a helpful way to store energy. Having levels that are too high, however, has long been linked to heart disease, though scientists have never definitively determined whether it was a cause or a signal.

“The results of our study highlight the potential usefulness of naturally occurring loss-of-function mutations in guiding the selection of therapeutic targets,” the researchers, led by Sekar Kathiresan, a cardiologist at Massachusetts General Hospital in Boston, said in one of the reports.

When working properly, APOC3 creates a protein that slows down removal of triglycerides from the blood to make sure the body has energy when it needs it. The mutations may allow the fat to be more quickly eliminated, the studies suggest. Creating drugs that mimic this action may be a natural next step, the scientists suggested.

Leading Killer

Despite advances that range from drugs that control bad cholesterol, such as the Pfizer Inc. statin Lipitor, and devices that help keep blood flowing, such as stents, heart disease remains the leading cause of death in the U.S., according to the Atlanta-based Centers for Disease Control and Prevention. It kills about 600,000 people yearly.

Kathiresan’s team sequenced genes in more than 3,734 people to identify the APOC3 mutations. They then expanded the genetic search to more than 100,000 people to determine a 40 percent lower risk profile among those who carried the variants.

A second study in more than 75,000 people, led by Anne Tybjaerg-Hansen of Copenhagen University Hospital, determined that people with the variants have a 44 percent drop in triglycerides. Their chance of having ischemic heart disease was 36 percent less than the general population, Tybjaerg-Hansen reported.

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