Two studies: identification of single gene mutation protects against heart attack

June 20, 2014

Two major studies published this week in The New England Journal of Medicine, funded by the National Institutes of Health and the European Union, independently identified mutations in a single gene that protect against heart attacks by keeping levels of triglycerides very low. Triglycerides have mystified researchers for some time, although they are routinely measured along with cholesterol in blood tests and are often high in people with heart disease. Many experts have been unconvinced, however, that they cause heart attacks. Now, the two studies have concluded that people with a genetic predisposition to elevated triglyceride levels have fewer heart attacks than those with genetically lower triglyceride levels.

The conclusions reported this week were first hinted at in 2008 in a study of Amish people. One in 20 of the Amish subjects had a mutation that destroys a gene involved in triglyceride metabolism, compared with one in 150 Americans generally, and the Amish have significantly fewer heart attacks. Scientists were intrigued, but they lacked the data to ascertain the gene’s role in heart attacks.

In one of the two latest studies, involving a general population, investigators began searching for the related genes. One gene, APOC3, stood out. The scientists found four mutations that destroyed the function of this gene. “Those who carry the gene mutations have a 40% reduction in triglyceride levels and a 40% lower risk of heart disease,” says lead researcher Sekar Kathiresan, PhD.

The second study, led by Anne Tybjaerg-Hansen, MD, showed that low triglyceride levels are linked to a reduced heart attack risk. Her team also asked whether people who had mutations destroying the APOC3 gene had fewer heart attacks. Those with such mutations had a 44% reduction in triglycerides and a 36% lower heart attack risk. Learn more from a New York Times story.

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