Related Experiment Video

Updated: Oct 16, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

8.3K

LDL-cholesterol and PCSK9 in patients with familial hypercholesterolemia: influence of PCSK9 variants under

Masato Hamasaki1, Naoki Sakane2, Kazuo Hara3

  • 1Division of Community and Family Medicine, Jichi Medical University, Shimotsuke-City, Japan.

Journal of Clinical Laboratory Analysis
|October 15, 2021
PubMed

Insights

Familial hypercholesterolemia (FH) patients with PCSK9 gain-of-function variants show a retained correlation between LDL cholesterol and PCSK9 levels, even with lipid-lowering therapy. These variants may guide additional statin treatment.

Area of Science:

  • Genetics and Cardiovascular Disease
  • Biochemistry and Molecular Biology

Background:

  • Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C), increasing coronary artery disease (CAD) risk.
  • The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is linked to FH, with a known correlation between LDL-C and PCSK9 levels in untreated individuals.

Purpose of the Study:

  • To investigate the correlation between LDL-C and PCSK9 levels in FH patients undergoing lipid-lowering therapy (LLT).
  • To determine if PCSK9 variants influence the LDL-C and PCSK9 relationship under LLT.

Main Methods:

  • A cohort of 70 FH patients on LLT was analyzed.
  • Next-generation sequencing was used to identify variants in LDLR, PCSK9, and APOB genes.
  • Correlation analysis was performed between LDL-C and PCSK9 levels based on identified variants.

Main Results:

  • A significant positive correlation (r = 0.79, p = 0.04) between LDL-C and PCSK9 levels was found specifically in FH patients with PCSK9 gain-of-function (GOF) variants (n=7).
  • This correlation was not observed in patients with LDLR variants (n=17) or variant-negative patients (n=46).
  • LDL-C and PCSK9 levels were comparable across groups with PCSK9 GOF, LDLR variants, and variant-negative FH patients.

Conclusions:

  • The correlation between LDL-C and PCSK9 levels persists in FH patients with PCSK9 GOF variants, even when on LLT.
  • PCSK9 GOF variants may serve as biomarkers for identifying FH patients who could benefit from intensified statin therapy.
Abstract

Keywords:
PCSK9 inhibitorgain-of-function mutationgenetic hypercholesterolemialipid-lowering therapylow-density lipoprotein receptorstatins

More Related Videos

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

13.7K
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

8.3K

Related Concept Videos

Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
960
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
63
Coronary Artery Disease IV: Preventive Measures01:26

Coronary Artery Disease IV: Preventive Measures

Effective preventive measures for coronary artery disease (CAD) focus on controlling modifiable risk factors, including cholesterol abnormalities and lifestyle changes.Cholesterol ManagementFirst, the Mediterranean diet and the American Heart Association advocate for maintaining low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, with a more stringent recommendation of below 70 mg/dL for individuals at high risk. LDL cholesterol, often termed "bad cholesterol," can lead to the...
396
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
752
Blood Studies for Cardiovascular System III: Serum Lipid Profile01:25

Blood Studies for Cardiovascular System III: Serum Lipid Profile

Understanding serum lipids is crucial for maintaining cardiovascular health and preventing heart disease and stroke.
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
348
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
24