Novel Insights in Genetic Mechanisms Underlying Cholesterol Uptak

April 28, 2023

The genetic variability greatly influences the LDL cholesterol levels and the atherosclerotic risk leading to coronary artery disease, a major cause of death and disability worldwide. 

A proper understanding of the genetic mechanisms underlying cholesterol serum levels and cholesterol uptake would provide a roadmap for further efforts in investigating treatment options for coronary artery disease and other conditions with high genetic component. 

“We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake.”