title: Carriers of the PCSK9 R46L Variant Are Characterized by an Antiatherogenic Lipoprotein Profile Assessed by Nuclear Magnetic Resonance Spectroscopy-Brief Report.
abstract: 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.
  
  
  
  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.
  
  
  
  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.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: Rutger
authors.initials: R
authors.lastname: Verbeek
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: Marjorie
authors.initials: M
authors.lastname: Boyer
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: From the Department of Vascular Medicine (R.V., G.K.H., J.J.P.K.) and Department of Cardiology (S.M.B.), Academic Medical Centre, Amsterdam, The Netherlands; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Canada (M.B., B.J.A.); Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada (M.B., B.J.A.); Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.W.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.). benoit.arsenault@criucpq.ulaval.ca.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004739:England; D005260:Female; D006579:Heterozygote; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D010641:Phenotype; D054497:Phospholipases A2, Secretory / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9 / Q000235:genetics*; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D054497:Phospholipases A2, Secretory; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: PCSK9; R46L; lipoprotein(a); lipoproteins; nuclear magnetic resonance spectroscopy