Carriers of the PCSK9 R46L Variant Are Characterized by an Antiatherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy-Brief Report
Arteriosclerosis, Thrombosis, and Vascular Biology
American Heart Association
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Verbeek, R., Boyer, M., Boekholdt, S., Hovingh, G., Kastelein, J., Wareham, N., Khaw, K., & et al. (2017). Carriers of the PCSK9 R46L Variant Are Characterized by an Antiatherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy-Brief Report. Arteriosclerosis, Thrombosis, and Vascular Biology, 37 (1), 43-48. https://doi.org/10.1161/ATVBAHA.116.307995
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.
PCSK9, R46L, lipoprotein(a), lipoproteins, nuclear magnetic resonance spectroscopy
The EPIC-Norfolk Study is funded by Cancer Research UK grant number 14136 and the Medical Research Council grant number G1000143. R.V. is supported by a grant from the European Union [TransCard: FP7-603091-2]. B.J.A. holds a junior scholar award from the Fonds de recherche du Québec: Santé (FRQS). J.J.P.K. is a recipient of the Dutch Heart Foundation Lifetime Achievement Award (2010).
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
MEDICAL RESEARCH COUNCIL (MR/N003284/1)
Medical Research Council (MC_U106179471)
External DOI: https://doi.org/10.1161/ATVBAHA.116.307995
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263519