title: Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia.
abstract: The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75(th) percentile (called "FH low") were selected, as well as those with LDL-C above the 90(th) percentile (called "FH high"). Relatives who tested negative for the mutation were the "controls." PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P = 0.50). Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.
authors.affiliation: Department of Vascular Medicine University of Amsterdam, Amsterdam, The Netherlands,. Electronic address: r.huijgen@amc.uva.nl.
authors.forename: R
authors.initials: R
authors.lastname: Huijgen
authors.affiliation: Department of Vascular Medicine University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S W
authors.initials: SW
authors.lastname: Fouchier
authors.affiliation: The Heart Research Institute, Sydney, NSW, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Denoun
authors.affiliation: Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: Hutten
authors.affiliation: Department of Vascular Medicine University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M N
authors.initials: MN
authors.lastname: Vissers
authors.affiliation: Faculté de Médecine, Inserm U957, Nantes, France.
authors.forename: G
authors.initials: G
authors.lastname: Lambert
authors.affiliation: Department of Vascular Medicine University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: J J P
authors.initials: JJP
authors.lastname: Kastelein
mesh_terms: D000293:Adolescent; D000328:Adult; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases