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Genetic Studies Help Unravel the Triglyceride Problem — Physician’s First Watch

Medical News |
June 19, 2014

Genetic Studies Help Unravel the Triglyceride Problem

By Larry Husten

Edited by Susan Sadoughi, MD, and Lorenzo Di Francesco, MD, FACP, FHM

Rare variations in a gene (APOC3) that encodes for apolipoprotein C3 are associated with reduced triglyceride levels and, in turn, lower risk for heart disease, according to two studies in the New England Journal of Medicine.

In the first, researchers sequenced the genes of some 3700 people and identified several rare loss-of-function variants of APOC3. As expected, people with the variants had significantly lower triglyceride levels. They 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, they write, "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.

The second study included over 75,000 participants in two large Danish prospective studies. 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.

Reader Comments (1)

paul helman,MD Physician, Internal Medicine, northshore university health system

That similarly low levels of triglycerides and raised HDL can be acieved in most anyone by carbohydrate restriction to produce physiologic ketosis.

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