Turns out 'good' cholesterol can at times be 'bad'

It turns out what's referred to as "good" cholesterol might actually put you at a much greater risk of heart disease.

The generally accepted medical maxim that elevated HDL cholesterol (HDL-C) is "good" has been overturned by a multi-center, international study, led by researchers from the the University of Pennsylvania.

They show that a certain genetic cause of increased HDL-C may actually be "bad," noting that a specific mutation in a gene which encodes a cell receptor protein that binds to HDL prevents the receptor from functioning.

The mutation causes an increased risk of coronary heart disease even in the presence of elevated levels of HDL-C or "good" cholesterol.

Senior author Daniel J. Rader said that the results indicate that some causes of raised HDL actually increase risk for heart disease. This is the first demonstration of a genetic mutation that raises HDL but increases risk of heart disease.

Rader and his colleagues sequenced the lipid-modifying regions of the genomes of 328 people with markedly elevated HDL (along with a control group with lower HDL) to identify genetic causes of high HDL. One of the genes they focused on was SCARB1, which encodes for Scavenger Receptor B1 (SR-B1), the major receptor for HDL on cell surfaces.

In the course of this sequencing, they identified, for the first time, a person without any SCARB1 function, typified by an extremely high HDL-C level of about 150 mg/dL, whereas the normal level is about 50 mg/dL. The subject had two copies of a SCARB1 mutation called P376L, which the team showed caused a breakdown in HDL receptor function.

Rader suggests 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.

He added, "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."

Their findings are published in Science.