Raise levels of “good” cholesterol while keeping “bad” cholesterol down – it’s Heart Health 101. But for some, having loads of good cholesterol is associated with higher risk of heart disease. And now, researchers have identified the pesky gene behind the paradox.
An international collaboration, led by Daniel Rader from the University of Pennsylvania, found the people missing one or two copies of the gene SCARB1 weren’t able to effectively use high-density lipoprotein (HDL) – the “good” form of cholesterol that usually protects the heart.
And while missing one or both SCARB1 gene copies is rare, the work, which was published their work in Science, could explain why some people taking HDL-boosting drugs can also have heart disease.
The role of HDL is to pick up and drag bad cholesterol – which lines arteries and clogs the cirulatory system – to the liver, which eliminates it. Studies in mice have shown this is made possible by the SR-B1 protein, which is made by the SCARB1 gene.
But drug clinical trials, which aim to raise levels of that cholesterol-shifting HDL, have mostly flopped.
So Rader and colleagues wondered if there might be a genetic effect. Do some people lack the SCARB1 gene?
They compared lipid-modifying genes in a group of 328 people with very high levels of HDL with a control group. One of the 328 high-HDL subjects, a 67-year-old woman, had no functioning copies of the SCARB1 gene. So while she had high levels of HDL in her blood, her arteries were clogged by more cholesterol than for a woman of her age.
When the researchers took a look at what removing the SCARB1 gene did to cells and mice, they saw their arteries become clogged with cholesterol, even while their HDL levels were high.
Using the Global Lipids Genetics Consortium of more than 300,000 people, they searched for those missing one or both copies of the gene. While rare, those who carried one functioning copy of SCARB1 had higher risk of heart disease compared to those who had two.
They weren’t able to find another individual without any copies at all.
Instead of taking HDL-boosting drugs, the researchers suggest targeting the protein coded by the SCARB1 gene: “Up-regulation or enhancement of SR-BI could be a novel therapeutic approach to reducing [coronary heart disease] risk in the general population.”