Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children

J Clin Lipidol. 2018 Jan-Feb;12(1):211-218. doi: 10.1016/j.jacl.2017.10.003. Epub 2017 Oct 12.

Abstract

Background: Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children.

Objectives: We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh).

Methods: This was a cross-sectional study performed in a Lipid Unit from a University hospital. The participants were 177 children distributed into FH (n = 77) and CCh (n = 100). Main outcomes were changes in IDOL, sLDLR, and PCSK9 plasma concentrations between children groups; secondary outcomes were the association between IDOL, sLDLR, and PCSK9 and lipid profile determined by 2-dimensional nuclear magnetic resonance.

Results: The IDOL levels were higher in FH compared with CCh (P = .007). The PCSK9 levels were elevated in FH (P < .001). The sLDLR levels had no significant differences between groups. IDOL was significantly positively associated to total and LDL cholesterol and ApoB100 but not to LDL particle number. However, a robust correlation with Lp(a) (P = .001) was observed. PCSK9 had the strongest correlation with LDL-associated parameters including particle number. sLDLR was associated with triglyceride levels (P < .001) and triglyceride-rich particles and inversely to LDL size.

Conclusions: The IDOL and PCSK9 plasma levels are significantly higher in FH children. Interestingly, sLDLR was associated with atherogenic dyslipidemia components. IDOL concentrations show a robust association with Lp(a) levels. To study the role of plasma biomarkers associated with LDLR expression in FH is warranted.

Keywords: 2D-1H-NMR; Children; Familial hypercholesterolemia; IDOL; LDL; LDLR; Lp(a); PCSK9; Triglyceride.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Area Under Curve
  • Biomarkers / blood*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / diagnosis*
  • Lipoprotein(a) / blood
  • Male
  • Proprotein Convertase 9 / blood*
  • ROC Curve
  • Receptors, LDL / blood*
  • Risk Factors

Substances

  • Biomarkers
  • Lipoprotein(a)
  • Receptors, LDL
  • PCSK9 protein, human
  • Proprotein Convertase 9