Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia

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...

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Published in:	Journal of lipid research Vol. 53; no. 5; pp. 979 - 983
Main Authors:	Huijgen, R., Fouchier, S.W., Denoun, M., Hutten, B.A., Vissers, M.N., Lambert, G., Kastelein, J.J.P.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-05-2012 The American Society for Biochemistry and Molecular Biology Elsevier
Subjects:	Adolescent Adult atherosclerosis Carotid Intima-Media Thickness Cholesterol, LDL - blood DNA Mutational Analysis Female gene expression Genetic Testing Humans Hyperlipoproteinemia Type II - blood Hyperlipoproteinemia Type II - genetics Hyperlipoproteinemia Type II - physiopathology low-density lipoprotein cholesterol Male Middle Aged Patient-Oriented and Epidemiological Research Phenotype Proprotein Convertase 9 proprotein convertase subtilisin kexin type 9 Proprotein Convertases - blood Serine Endopeptidases - blood Young Adult atherosclerosis proprotein convertase subtilisin kexin type 9 low-density lipoprotein cholesterol gene expression
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Summary:	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 75th percentile (called “FH low”) were selected, as well as those with LDL-C above the 90th 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.P023994