Genetic and Metabolic Determinants of Plasma PCSK9 Levels
Genetic and Metabolic Determinants of Plasma PCSK9 Levels
复制标题
DOI：
10.1210/jc.2009-0141
复制
发表时间：
2009-07-01
影响因子：
5.8
通讯作者：
Hobbs, Helen H.
中科院分区：
文献类型：
--
作者：
Lakoski, Susan G.;Lagace, Thomas A.;Hobbs, Helen H.
内容：PCSK 9是一种分泌性蛋白质，可影响血浆低密度脂蛋白胆固醇（LDL-C）水平和冠心病易感性。PCSK 9存在于人血浆中，但导致PCSK 9血浆浓度差异的因素以及它们如何影响脂蛋白水平尚未得到很好的表征。目的：本研究的目的是测量大的种族多样性人群中的PCSK 9水平设计：我们在达拉斯心脏研究中进行了一项观察性研究，该研究是达拉斯县的一项多种族、基于概率的样本。PCSK 9的血浆水平变化范围约为100倍（33-2988 ng/ml;中位数为487 ng/ml）。无论雌激素状态如何，女性（517 ng/ml）的水平显著高于男性（450 ng/ml），绝经后女性显著高于绝经前女性（P < 0.0001）。PCSK 9的血浆水平与LDL-C的血浆水平相关（r = 0.24），但解释LDL-C水平变异的比例小于8%（r（2）= 0.073）。与PCSK 9水平相关的其他因素包括甘油三酯、胰岛素和葡萄糖的血浆水平。PCSK 9功能缺失突变和血浆LDL-C水平降低的个体在校正年龄、性别和LDL-C水平后，血浆PCSK 9水平也显著降低（P < 0.0001）。结论：多种代谢和遗传因素导致了普通人群血浆PCSK 9水平的变化。尽管PCSK 9水平与LDL-C血浆水平相关，但它们仅占该脂蛋白水平变化的一小部分。（临床内分泌代谢杂志94：2537-2543，2009）
Context: PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease. PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized.Objective: The aim of the study was to measure PCSK9 levels in a large, ethnically diverse population (n = 3138) utilizing a sensitive and specific sandwich ELISA.Design: We conducted an observational study in the Dallas Heart Study, a multiethnic, probability-based sample of Dallas County.Results: Plasma levels of PCSK9 varied over approximately 100-fold range (33-2988 ng/ml; median, 487 ng/ml). Levels were significantly higher in women (517 ng/ml) than in men (450 ng/ml), and in postmenopausal women compared to premenopausal women (P < 0.0001), irrespective of estrogen status. Plasma levels of PCSK9 correlated with plasma levels of LDL-C (r = 0.24) but explained less than 8% of the variation in LDL-C levels (r(2) = 0.073). Other factors that correlated with PCSK9 levels included plasma levels of triglycerides, insulin, and glucose. Individuals with loss-of-function mutations in PCSK9 and reduced plasma levels of LDL-C also had significantly lower plasma levels of PCSK9 after adjusting for age, gender, and LDL-C levels (P < 0.0001).Conclusion: Multiple metabolic and genetic factors contribute to variation in plasma levels of PCSK9 in the general population. Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein. (J Clin Endocrinol Metab 94: 2537-2543, 2009)