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标题：Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia
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作者：R. Huijgen ; S. W. Fouchier ; M. Denoun 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：5
页码：979-983
DOI：10.1194/jlr.P023994
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
关键词：proprotein convertase subtilisin kexin type 9 ; atherosclerosis ; low-density lipoprotein cholesterol ; gene expression