University of Maryland School of Medicine Researchers Lead Way on APOC3 Research

For immediate release: June 19, 2014

Two major studies published Wednesday in the New England Journal of Medicine have identified mutations in the APOC3 gene that help to prevent heart attacks by reducing the level of triglycerides in the blood. The research by scientists in Boston and Copenhagen builds on earlier research by a team of researchers at the University of Maryland School of Medicine led by Toni I. Pollin, M.S., Ph.D., associate professor of medicine and epidemiology & public health. The University of Maryland School of Medicine research is featured in the New York Times.

The University of Maryland researchers reported in the journal Science in December 2008 that they had discovered a novel mutation of the APOC3 gene in about 5 percent of the Old Order Amish population that significantly reduced triglyceride levels and appeared to help prevent cardiovascular disease. Carriers of the mutation have half the amount of apoC-III, a protein linked to triglycerides, than people without the gene variant.

Dr. Pollin noted that those with this mutation of the APOC3 gene had higher levels of HDL-cholesterol, the so-called “good” cholesterol, and lower levels of LDL-cholesterol, the “bad” cholesterol. In addition, they had less arteriosclerosis (hardening of the arteries) – as measured by the amount of calcium in their coronary arteries. “Our findings suggest that having a lifelong deficiency of apoC-III helps to protect people from developing cardiovascular disease,” she said in 2008. Click here for more details about  the research.

A team led by cardiologist Sekar Kathiresan, M.D., of Massachusetts General Hospital and the Broad Institute, has now reported in the New England Journal of Medicine that people with rare mutations of the APOC3 gene have dramatically lower levels of triglycerides and were 40 percent less likely to have heart disease than those without the mutation. Another study led by a group of Danish researchers also identified mutations in the same gene and a decreased risk of heart disease.

Michael Miller, M.D., professor of cardiology and epidemiology and preventive medicine at the University of Maryland School of Medicine and director of the Center of Preventive Cardiology at the University of Maryland Medical Center, says this latest research emphasizes the importance of triglycerides in heart disease risk assessment.

“Studies from the University of Maryland dating back to 1998 have suggested that low triglyceride levels are associated with a reduced risk of heart attacks,” says Dr. Miller, noting the new research is consistent with a scientific statement by an American Heart Association committee that he chaired in 2011 that a triglyceride level less than 100 is optimal. “We now have evidence based on Dr. Pollin's study in the Amish and the two new studies that genetically low triglyceride is good for the heart,” Dr. Miller says.