Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents.
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) microg/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. .
Baass
Alexis
A
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montréal, Québec, Canada.
Dubuc
Geneviève
G
Tremblay
Michel
M
Delvin
Edgard E
EE
O'Loughlin
Jennifer
J
Levy
Emile
E
Davignon
Jean
J
Lambert
Marie
M
D000293:Adolescent; D000367:Age Factors; D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D050171:Dyslipidemias / Q000097:blood* / Q000453:epidemiology; D005215:Fasting; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D011792:Quebec / Q000453:epidemiology; D012697:Serine Endopeptidases / Q000097:blood*; D012737:Sex Factors
D001053:Apolipoproteins; D015415:Biomarkers; D008055:Lipids; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases