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. 2017 Jan;37(1):43-48.
doi: 10.1161/ATVBAHA.116.307995. Epub 2016 Nov 17.

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

Rutger Verbeek  1 , Marjorie Boyer  1 , S Matthijs Boekholdt  1 , G Kees Hovingh  1 , John J P Kastelein  1 , Nicholas Wareham  1 , Kay-Tee Khaw  1 , Benoit J Arsenault  2
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Carriers of the PCSK9 R46L Variant Are Characterized by an Antiatherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy-Brief Report

Rutger Verbeek et al. Arterioscler Thromb Vasc Biol. 2017 Jan.

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.

Keywords: PCSK9; R46L; lipoprotein(a); lipoproteins; nuclear magnetic resonance spectroscopy.

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Conflict of interest statement

Disclosures: no potential conflicts of interests.

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