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Severance finds possible therapeutic agent for atherosclerosis
  • By Marian Chu
  • Published 2018.05.25 16:00
  • Updated 2018.05.25 16:00
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Professors Lee Sang-hak (left) and Gee Heon-yung

Researchers have discovered variants of the CDKAL1 gene is involved in the removal of cholesterol in the blood, raising the possibility of developing a therapeutic agent for atherosclerosis.

Atherosclerosis is a disease where cholesterol and plaque build up inside the arteries and, when severe, can lead to conditions such as angina, coronary artery disease, and heart attacks.

High-density lipoprotein (HDL), or the so-called good cholesterol, helps remove bad cholesterol as it moves down the bloodstream, thereby keeping conditions such as atherosclerosis at bay. Despite the importance of the good cholesterol, there has been little research that studied genes related to HDL function, Severance said.

The joint team, led by Professor Lee Sang-hak from Severance Hospital’s Department of Cardiology and Professor Gee Heon-yung from the Department of Pharmacology at Yonsei University College of Medicine, aimed to look at the genes associated with HDL function.

In particular, researchers aimed to identify genes that impact cholesterol efflux capacity (CEC) – a measure of how well HLD removes cholesterol from cells. People with high CEC levels are known to be at low risk for cardiovascular disease, Severance said.

Using full-length genomic association studies, the team examined genetic mutations related to CEC in 607 individuals with coronary artery disease and 158 patients in an independent replication group.

Findings from the discovery group of 607 subjects showed 631 genetic variants have a significant association with CEC levels. The study was replicated in 158 subjects to find five genetic variants correlated with CEC, according to the researchers.

After adjusting for clinical and laboratory variables, researchers found four variants of the CDKAL1 gene maintained a significant relationship with CEC.

“This is the first time to discover a gene related to CEC. Patients with one of the four genetic variants had a better CEC function and a lower risk of atherosclerosis than those without any of the mutations,” Professor Lee said.

Researchers said they expect a higher possibility for developing a therapeutic agent for atherosclerosis with study findings.

These results were published in the latest edition of the European atherosclerosis journal, Atherosclerosis.


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