Baass Alexis, Dubuc Geneviève, Tremblay Michel, Delvin Edgard E, O'Loughlin Jennifer, Levy Emile, Davignon Jean, Lambert Marie
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montréal, Québec, Canada.
Clin Chem. 2009 Sep;55(9):1637-45. doi: 10.1373/clinchem.2009.126987. Epub 2009 Jul 23.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein convertase that posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLR) in hepatocytes and increases plasma LDL cholesterol (LDL-C). Heterozygote gain-of-function mutations of PCSK9 are associated with the familial hypercholesterolemia phenotype, whereas loss-of-function variants are associated with reduced LDL-C concentrations and lower coronary risk. Plasma PCSK9 correlates with body mass index, triglyceridemia, total cholesterol, and LDL-C in adults, but no data are available in youth.
We studied 1739 French Canadian youth ages 9, 13, and 16 years who participated in the Quebec Child and Adolescent Health and Social Survey, a province-wide school-based survey conducted in 1999. An ELISA assay was used to measure plasma PSCK9.
The mean (SD) plasma PCSK9 concentration was 84.7 (24.7) microg/L in the sample. In boys, plasma PCSK9 decreased with age, whereas the inverse was true for girls. There were statistically significant positive associations between PCSK9 and fasting glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). In multivariable analysis, a 10% higher fasting insulin was associated with a 1%-2% higher PCSK9 in both sexes. There were also positive associations between PCSK9 and total cholesterol, LDL-C, and triglycerides, as well as with HDL-C and apolipoproteins A1 and B.
PCSK9 is associated with age, sex, and multiple metabolic markers in youth. A novel finding is that PCSK9 is associated with fasting insulinemia, which suggests that PCSK9 could play a role in the development of dyslipidemia associated with the metabolic syndrome. .
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）是一种蛋白转化酶，可在翻译后促进肝细胞中低密度脂蛋白受体（LDLR）的降解，并增加血浆低密度脂蛋白胆固醇（LDL-C）水平。PCSK9的杂合子功能获得性突变与家族性高胆固醇血症表型相关，而功能丧失性变体与LDL-C浓度降低和较低的冠心病风险相关。成人血浆PCSK9与体重指数、甘油三酯血症、总胆固醇和LDL-C相关，但青少年中尚无相关数据。
我们研究了1739名年龄分别为9岁、13岁和16岁的法裔加拿大青少年，他们参与了1999年在魁北克省开展的一项全省范围的基于学校的魁北克儿童与青少年健康及社会调查。采用酶联免疫吸附测定法（ELISA）测量血浆PCSK9。
样本中血浆PCSK9的平均（标准差）浓度为84.7（24.7）μg/L。在男孩中，血浆PCSK9随年龄降低，而女孩则相反。PCSK9与空腹血糖、胰岛素和HOMA-IR（胰岛素抵抗稳态模型评估）之间存在统计学显著的正相关。在多变量分析中，空腹胰岛素水平每升高10%，男女的PCSK9水平均升高1%-2%。PCSK9与总胆固醇、LDL-C和甘油三酯之间也存在正相关，同时与高密度脂蛋白胆固醇（HDL-C）以及载脂蛋白A1和B也存在正相关。
PCSK9与青少年的年龄、性别及多种代谢指标相关。一个新发现是PCSK9与空腹胰岛素血症相关,这表明PCSK9可能在与代谢综合征相关的血脂异常发展中起作用。
