Clinical Chemistry
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Clinical Chemistry 55: 1637-1645, 2009. First published July 23, 2009; 10.1373/clinchem.2009.126987
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(Clinical Chemistry. 2009;55:1637-1645.)
© 2009 American Association for Clinical Chemistry, Inc.

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Plasma PCSK9 Is Associated with Age, Sex, and Multiple Metabolic Markers in a Population-Based Sample of Children and Adolescents

Alexis Baass1,2, Geneviève Dubuc1,2, Michel Tremblay1, Edgard E. Delvin2, Jennifer O'Loughlin5, Emile Levy3, Jean Davignon1 and Marie Lambert4,a

1 Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal (IRCM), Montréal, Québec, Canada; Departments of 2 Clinical Biochemistry, 3 Nutrition, and 4 Pediatrics, CHU Sainte-Justine and Université de Montréal, Montréal, Québec, Canada; 5 Department of Social and Preventive Medicine, Université de Montréal, Montréal, Québec, Canada.

aAddress correspondence to this author at: Medical Genetics Service, CHU Sainte-Justine, 3175 Côte-Sainte-Catherine, Montréal, Québec, Canada, H3T 1C5. Fax +514-345-4766; e-mail marie.lambert{at}umontreal.ca.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein convertase that posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLR) in hepatocytes and increases plasma LDL cholesterol (LDL-C). Heterozygote gain-of-function mutations of PCSK9 are associated with the familial hypercholesterolemia phenotype, whereas loss-of-function variants are associated with reduced LDL-C concentrations and lower coronary risk. Plasma PCSK9 correlates with body mass index, triglyceridemia, total cholesterol, and LDL-C in adults, but no data are available in youth.

Methods: We studied 1739 French Canadian youth ages 9, 13, and 16 years who participated in the Quebec Child and Adolescent Health and Social Survey, a province-wide school-based survey conducted in 1999. An ELISA assay was used to measure plasma PSCK9.

Results: The mean (SD) plasma PCSK9 concentration was 84.7 (24.7) µg/L in the sample. In boys, plasma PCSK9 decreased with age, whereas the inverse was true for girls. There were statistically significant positive associations between PCSK9 and fasting glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). In multivariable analysis, a 10% higher fasting insulin was associated with a 1%–2% higher PCSK9 in both sexes. There were also positive associations between PCSK9 and total cholesterol, LDL-C, and triglycerides, as well as with HDL-C and apolipoproteins A1 and B.

Conclusions: PCSK9 is associated with age, sex, and multiple metabolic markers in youth. A novel finding is that PCSK9 is associated with fasting insulinemia, which suggests that PCSK9 could play a role in the development of dyslipidemia associated with the metabolic syndrome. .






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Copyright © 2009 by the American Association for Clinical Chemistry.