Gene Variant Reduces Cholesterol by 2 Mechanisms: Research

Increased risk for coronary heart diseases in those people with high levels of low-density lipoprotein (LDL) cholesterol. A variant in the human gene encoding the protein sortilin is associated with reduced plasma LDL levels and a decreased risk of heart attack. This variant results in markedly higher sortilin protein expression in liver.

Dr. Daniel Rader and colleagues at the University of Pennsylvania in Philadelphia have uncovered a two-pronged mechanism for the change in LDL observed. Using a mouse model system, the Rader team found that increased liver sortilin is responsible for reducing secretion of APOB, a protein that transports LDL to tissue, and also triggers LDL breakdown. Both of these effects were dependent on a cellular process known as lysosomal targeting. Their data provide functional evidence that genetically-increased hepatic sortilin in humans reduces LDL by increasing LDL degradation, thus removing LDL from circulation, as well as decreasing APOB.

Source-Eurekalert