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The Triglycerides of the Matter

A pair of studies appearing in the New England Journal of Medicine yesterday has linked variants in the APOC3 gene to lower triglyceride levels and reduced risk of heart attack, the New York Times reports.

"Triglycerides have long puzzled researchers, although they are routinely measured along with cholesterol in blood tests and are often high in people with heart disease. Many experts were unconvinced they caused heart attacks," the Times notes.

In one of the studies, researchers led by Sekar Kathiresan from Massachusetts General Hospital and the Broad Institute examined the protein-coding gene sequences of some 3,700 Americans. From this, they uncovered that rare mutations in the apolipoprotein C3 (APOC3) gene were associated with lower plasma triglyceride levels, and people carrying those mutations had a 40 percent lower risk of coronary artery disease.

In the other NEJM study, Anne Tybjærg-Hansen at the University of Copenhagen and her colleagues examined in a cohort of more than 75,700 people whether low nonfasting triglycerides levels were linked to a reduced risk of ischemic vascular disease and ischemic heart disease and whether loss of function mutations in APOC3 were associated with low levels of nonfasting triglycerides and reduced disease risk. And indeed, they reported that loss-of-function mutations in APOC3 were linked to lower triglyceride levels and reduced ischemic cardiovascular disease risk.

The Times notes that the company Isis has been interested in this gene, and has developed a drug that appears to be able to reduce triglyceride levels by some 70 percent.

"It is the most important drug in our pipeline," Stanley Crooke, the chief executive of Isis, tells the Times. "Trust me, these data are really exciting."