'Good' cholesterol not always protective for heart: study
"This results in reduced clearance of peripheral cholesterol through reverse cholesterol transport, increased furring of arteries (atherosclerosis) and an increase in risk of coronary heart disease," Holmes said in a statement.
The researchers also searched for this genetic mutation using Global Lipid Genetics Consortium data from more than 300,000 individuals.
The SCARB1 variant was found to be rare in the population, but carriers had significantly higher HDL levels.
Notably, people who carry one copy of the SCARB1 variant have a higher risk of coronary heart disease compared with non-carriers.
Rader suggested that a therapeutic approach to increase the expression or activity of SCARB1 could be a new way to reduce the risk of heart disease even though it would reduce HDL blood levels.
"The work demonstrates that the protective effects of HDL are more dependent upon how it functions than merely how much of it is present," Rader concluded. "We still have a lot to learn about the relationship between HDL function and heart disease risk."
Previous research also raised the possibility that HDL might not be quite as protective against heart disease as generally believed by cardiologists, especially after several clinical trials of drugs that raised HDL levels showed little or no effect.