Rare Genetic Mutations Decrease Risk of Heart Disease

On Wednesday, researchers from the Massachusetts General Hospital announced their discovery of gene mutations that carry the potential to prevent heart attacks. These four incredibly rare gene mutations can lower the risk of coronary heart disease by as much as 40 percent, according to the results of two major studies, published in the New England Journal of Medicine.

"The combination of our genetic results, together with recent clinical trials of drugs that raised HDL levels but failed to prevent heart disease, are turning decades of conventional wisdom on its head," said senior author Sekar Kathiresan, a Broad associate member and director of preventive cardiology at Massachusetts General Hospital, in a news release. "HDL and triglycerides are both correlated with heart attack, and have an inverse relationship with one another-the lower the HDL, the higher the triglycerides. It has long been presumed that low HDL is the causal factor in heart disease, and triglycerides are along for the ride. But our genetic data indicate that the true causal factor may not be HDL after all, but triglycerides."

The study examined the biological role of triglycerides and their contribution to growing studies that focus on high triglyceride levels and increased risk of heart disease.

"Based on our findings, we predict that lowering triglycerides specifically through inhibition of APOC3 would have a beneficial effect by lowering disease risk," added senior co-author Alex Reiner, a member of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center and a research professor of epidemiology at the University of Washington's School of Public Health, in the news release. "Although statins remain a powerful arrow in the quiver, the notion of residual risk of coronary heart disease continues to be a significant clinical problem," added Kathiresan, in the press release. "Our study really reinvigorates the idea of lowering triglycerides and specifically, by blocking APOC3, as a viable therapeutic strategy for addressing residual risk."