Josefa Girona1, Cèlia Rodríguez-Borjabad1, Daiana Ibarretxe1, Mercedes Heras1, Nuria Amigo2, Albert Feliu3, Luis Masana4, Nuria Plana1. 1. Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. 2. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain; Biosfer Teslab, Reus and Department of Electronic Engineering, Universitat Rovira i Virgili, IISPV, Tarragona, Spain. 3. Pediatrics Research Unit, Universitat Rovira i Virgili, IISPV, Reus, Spain. 4. Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. Electronic address: luis.masana@urv.cat.
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.
BACKGROUND:Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FHchildren. 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 FHchildren. 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.
Authors: Yu-Jeong Choi; Sol Ji Lee; Hyo In Kim; Hee Jung Lee; So Jung Kang; Tai Young Kim; Chunhoo Cheon; Seong-Gyu Ko Journal: Sci Rep Date: 2020-11-16 Impact factor: 4.379