July 4, 2012
Gene Variant That Lowers Cholesterol?
(Ivanhoe Newswire) —It is known that high levels of low-density lipoprotein (LDL) cholesterol increase the risk for coronary heart disease. Now, researchers have discovered further insights about how a certain gene variant uses two mechanisms to reduce cholesterol.
A variant in the human gene that encodes the protein sortilin is linked with reduced plasma LDL levels and a decreased risk of heart attack. This variant results in noticeably higher sortilin protein expression in liver.
Dr. Daniel Rader and colleagues at the University of Pennsylvania in Philadelphia have discovered a two-pronged mechanism for the observed change in LDL. Using a mouse model system, the Rader team learned that increased liver sortilin reduces secretion of APOB, a protein that transports LDL to tissue and triggers LDL breakdown.
Both effects were reliant on a cellular process called lysosomal targeting. Their data provide useful evidence that genetically-increased hepatic sortilin in humans reduces LDL by increasing LDL degradation, which removes LDL from circulation and decreases APOB.
Source: Journal of Clinical Investigation