A Gene That Protects You From Heart Attack?

Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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Triglycerides are free fatty acids circulating in your blood. When you have your cholesterol panel checked with your doc you will see: triglycerides, HDL cholesterol and LDL cholesterol. Triglycerides fluctuate depending on what you have to eat or drink but normal fasting triglycerides are < 160. Unlike with LDL cholesterol, studies haven’t shown that high triglycerides are an important marker of risk of stroke and heart disease. That is why the findings of this gene are interesting, and surprising.

What did they look for?

Genes from 3734 people were tested for mutations associated with triglyceride levels in their blood. The authors of this study also looked at whether the same mutation that raised triglycerides was associated with heart disease.

What did they find?

The gene most strongly associated with blood triglyceride levels is a gene that codes apolipoprotein C3 (APOC3). LOSS of function of this gene was a good thing, and 1 in 150 persons carried a mutation that caused loss of APOC3 function, lucky them. If you carry one of the loss of function genes you had lower triglycerides (33% lower), higher HDL levels (the “good cholesterol”) and lower LDL levels.

Take home message.

In people who had lower circulating APOC3 levels, their risk of heart disease was reduced by 40%. So LOSS of APOC3 function protects you from heart disease.

Why is this surprising?

Well, because studies done using medications that lower triglycerides (Tricor, fenofibrate, gemfibrozil, fish oils) have failed to show a reduced risk of heart disease. In other words, lowering triglycerides with medications has never been shown to lower your risk of heart attack.

Why is the “loss of function of APOC3” protective exactly?

We don’t know why. You see, having this loss of function gene does a few things for you: lower triglycerides, higher HDL cholesterol and lower LDL cholesterol All of those are good things. Which of those three is protecting you from heart disease we aren’t sure.

The future:

What is cool is that medications down the line can target this loss-of-function APOC3 gene, leading to therapies that reduce risk of heart disease. What scientists will hope to come up with next are monoclonal antibodies that target APOC3. Now that, would be cool.

Dr O.

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