The aim of the present study was to investigate the relationship between circulating PCSK9 (proprotein convertase subtilisin kexin type 9) and FCHL (familial combined hyperlipidaemia) and, when positive, to determine the strength of its heritability. Plasma PCSK9 levels were measured in FCHL patients (n=45), NL (normolipidaemic) relatives (n=139) and their spouses (n=72). In addition, 11 FCHL patients were treated with atorvastatin to study the response in PCSK9 levels. PCSK9 levels were higher in FCHL patients compared with NL relatives and spouses: 96.1 compared with 78.7 and 82.0 ng/ml (P=0.004 and P=0.002 respectively). PCSK9 was significantly associated with both TAG (triacylglycerol) and apolipoprotein B levels (P<0.001). The latter relationship was accounted for by LDL (low-density lipoprotein)–apolipoprotein B (r=0.31, P=0.02), not by VLDL (very-low-density lipoprotein)–apolipoprotein B (r=0.09, P=0.49) in a subgroup of subjects (n=59). Heritability calculations for PCSK9 using SOLAR and FCOR software yielded estimates of 67–84% respectively (P<0.0001). PCSK9 increased from 122 to 150 ng/ml in 11 FCHL patients treated with atorvastatin (40 mg) once daily for 8 weeks (P=0.018). In conclusion, plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results, combined with the significant rise in PCSK9 levels after statin therapy, warrant further studies in order to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidaemia.
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Research Article|
July 12 2011
Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia
Martijn C.G.J. Brouwers;
*Department of Internal Medicine, Division of General Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
†Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
‡Laboratory of Metabolism and Vascular Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
Correspondence: Mr Martijn C.G.J. Brouwers (email [email protected]).
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Marleen M.J. van Greevenbroek;
Marleen M.J. van Greevenbroek
*Department of Internal Medicine, Division of General Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
‡Laboratory of Metabolism and Vascular Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
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Jason S. Troutt;
Jason S. Troutt
§Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, U.S.A.
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Angela Bonner Freeman;
Angela Bonner Freeman
§Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, U.S.A.
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Ake Lu;
Ake Lu
‖Departments of Human Genetics and Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, U.S.A.
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Nicolaas C. Schaper;
Nicolaas C. Schaper
†Department of Internal Medicine, Division of Endocrinology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
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Robert J. Konrad;
Robert J. Konrad
§Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, U.S.A.
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Coen D.A. Stehouwer
Coen D.A. Stehouwer
*Department of Internal Medicine, Division of General Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
‡Laboratory of Metabolism and Vascular Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
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Publisher: Portland Press Ltd
Received:
March 14 2011
Revision Received:
April 18 2011
Accepted:
May 03 2011
Accepted Manuscript online:
May 03 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (9): 397–403.
Article history
Received:
March 14 2011
Revision Received:
April 18 2011
Accepted:
May 03 2011
Accepted Manuscript online:
May 03 2011
Citation
Martijn C.G.J. Brouwers, Marleen M.J. van Greevenbroek, Jason S. Troutt, Angela Bonner Freeman, Ake Lu, Nicolaas C. Schaper, Robert J. Konrad, Coen D.A. Stehouwer; Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia. Clin Sci (Lond) 1 November 2011; 121 (9): 397–403. doi: https://doi.org/10.1042/CS20110129
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