HDL cholesterol (HDL-C), or "good" cholesterol, carries excess cholesterol – that might otherwise block arteries – from blood vessels back to the liver for processing and elimination. As such, individuals with high plasma HDL-C levels have a decreased risk of developing coronary artery disease. Genetics contribute to determining a person's plasma HDL-C level, and in a new JCI study Daniel Rader and colleagues from the University of Pennsylvania show that mutations in the LIPG gene, which codes for an enzyme known as endothelial lipase, result in high plasma HDL-C levels.
The authors examined the LIPG gene in 585 subjects of European ancestry and identified 10 people with previously unreported rare mutated forms of this gene that were unique to subjects with very high HDL-C levels. Further studies revealed that mutations in the LIPG gene that cause loss of endothelial lipase activity were the cause of increased plasma HDL-C levels. These data provide important human genetic evidence that inhibition of endothelial lipase is likely to raise HDL-C levels in humans. Whether or not the resulting increase in HDL-C level due to this inhibition would impact cardiovascular health requires further study.
TITLE: Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans
AUTHOR CONTACT:
Daniel J. Rader
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: (215) 573-4176; Fax: (215) 573-8606; E-mail: rader@mail.med.upenn.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=37176
Journal of Clinical Investigation