The genetic mutation found by researchers prevents cholesterol from being cleared, increasing the risk for heart disease. Photo by decade3d - anatomy online/Shutterstock
WASHINGTON, March 11 (UPI) -- Elevated levels of "good" cholesterol may not be good for everyone, according to a large study conducted in the United States and Europe.
Researchers in the international trial found a somewhat rare genetic mutation turns on its head the generally accepted idea that HDL-C, or "good" cholesterol, helps to protect against heart disease.
Generally, HDL-C helps remove cholesterol from arteries, but a mutation to SCARB1 prevents it from doing so, disrupting the body's ability to send bad cholesterol to the liver, where it is eliminated.
This, researchers said, actually increases the risk for heart disease among people genetically predisposed to have high HDL-C levels.
"This is an important study that sheds light on one of the major puzzles relating to cholesterol and heart disease, which is that despite strong evidence showing HDL-C reduces heart disease risk, clinical trials on the effects of HDL-C-raising drugs have been disappointing," Dr. Peter Weissberg, medical director for the British Heart Foundation, said in a press release. "These new findings suggest that the way in which HDL-C is handled by the body is more important in determining risk of a heart attack than the levels of HDL-C in the blood."
For the study, published in the journal Science, the researchers recruited 328 people with high HDL-C, as well as a group with lower levels of it, sequencing the lipid-modifying regions of each of their genomes.
The researchers found a person whose body did not make any SCARB1, explaining his HDL-C levels of nearly three times normal. Generating induced pluripotent stem cells from the person, the researchers created liver cells where they could see the difference between no SCARB1 function, and how it appeared in other participants.
HDL, or 'good' cholesterol, can remove cholesterol from arteries and shuttle it to the liver where it is eliminated, but this process can be disrupted in certain circumstances, such as deficiency of SCARB1. Photo by Daniel Rader/University of Pennsylvania
"The work demonstrates that the protective effects of HDL are more dependent upon how it functions than merely how much of it is present," Dr. Daniel Rader, chair of the genetics department at the University of Pennsylvania, said in a press release. "We still have a lot to learn about the relationship between HDL function and heart disease risk. Eventually we may want to perform genetic testing in persons with high HDL to make sure they don't have mutations -- like this one -- that raise HDL but don't protect against, or may even increase, risk for heart disease."