June 19th, 2014

Genetic Studies May Help Unravel the Triglyceride Problem

The precise role of triglycerides in heart disease has been very difficult to determine. To help untangle the knotty problem two research groups studied large populations and identified rare variations in a gene (APOC3) that encodes for apolipoprotein C3, which is known to increase triglyceride levels.

In the first paper, published in the New England Journal of Medicinean NHLBI working group sequenced the genes of 3,734 people and identified several rare loss-of-function variants of APOC3. As expected, people with the variants had significantly lower triglyceride levels. The researchers then analyzed data from more than 110,000 participants in 14 studies and observed that people with the same loss-of-function mutations had a 40% lower risk for coronary heart disease.

The results, write the authors, “show that loss of APOC3 function confers protection against clinical coronary heart disease,” though they were unable to identify a primary mechanism linking APOC3 to heart disease.

In the second paper, also published in the New England Journal of Medicine, researchers used data from more than 75,000 participants in two large Danish prospective studies to explore the role of APOC3. People with APOC3 loss-of-function mutations had triglyceride levels reduced by 44%, with corresponding risk reductions of 41% for ischemic vascular disease and 36% for ischemic heart disease.

In both studies the APOC3 mutations were also linked to elevated HDL levels and other changes in lipid values. The authors of both papers write that their findings suggest that APOC3 might make for an attractive drug target.

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