Carriers of the PCSK9 R46L Variant Are Characterized by an Antiatherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy-Brief Report.

Abstract

OBJECTIVE:

Carriers of the PCSK9 (proprotein convertase subtilisin/kexin 9) R46L genetic variant (rs11591147) are characterized by low levels of low-density lipoprotein cholesterol and a decreased risk of cardiovascular disease. We studied the impact of the R46L variant on lipoprotein size and composition.

APPROACH AND RESULTS:

Lipoprotein size and composition were measured by nuclear magnetic resonance spectroscopy in 2373 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. After adjusting for age, sex, and cardiovascular disease status, carriers of the R46L variant (n=77) were characterized by lower concentrations of very low-density lipoprotein particles (85.8±26.2 versus 99.0±33.3 nmol/L; P<0.001), low-density lipoprotein particles (1479.7±396.8 versus 1662.9±458.3 nmol/L; P<0.001), and lipoprotein(a) (11.1 [7.2-28.6] versus 12.4 [6.7-29.1] mg/dL; P<0.001) compared with noncarriers. Total high-density lipoprotein particle and very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particle sizes were comparable in carriers and noncarriers. Carriers were characterized by lower secretory phospholipase A2 (4.2±0.9 versus 4.6±1.3 nmol/mL/min; P=0.004) and lipoprotein-associated phospholipase A2 activity (47.5±14.1 versus 52.4±16.2 nmol/mL/min; P=0.02) compared with noncarriers.

CONCLUSIONS:

Results of this study suggest that carriers of the PCSK9 R46L genetic variant have lower very low-density lipoprotein and low-density lipoprotein particle concentrations, lower lipoprotein(a) levels, and lower secretory phospholipase A2 and lipoprotein-associated phospholipase A2 activity compared with noncarriers.

• Authors: Rutger Verbeek, Marjorie Boyer, S Matthijs Boekholdt, G Kees Hovingh, John J P Kastelein, Nicholas Wareham, Kay-Tee Khaw, Benoit J Arsenault
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 37 Issue 1 Pg. 43-48 (01 2017) ISSN: 1524-4636 [Electronic] United States
• PMID: 27856457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Heart Association, Inc.

Chemical References

• Biomarkers
• Lipoprotein(a)
• Lipoproteins
• Lipoproteins, LDL
• Lipoproteins, VLDL
• Phospholipases A2, Secretory
• 1-Alkyl-2-acetylglycerophosphocholine Esterase
• PLA2G7 protein, human
• PCSK9 protein, human
• Proprotein Convertase 9

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (blood)
• Aged
• Atherosclerosis (blood, enzymology, genetics, prevention & control)
• Biomarkers (blood)
• Case-Control Studies
• England
• Female
• Heterozygote
• Humans
• Lipoprotein(a) (blood)
• Lipoproteins (blood)
• Lipoproteins, LDL (blood)
• Lipoproteins, VLDL (blood)
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Particle Size
• Phenotype
• Phospholipases A2, Secretory (blood)
• Polymorphism, Single Nucleotide
• Proprotein Convertase 9 (genetics)
• Prospective Studies
• Protective Factors
• Risk Assessment
• Risk Factors