Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children
Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children
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DOI：
10.1016/j.jacl.2017.10.003
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发表时间：
2018-02-01
影响因子：
4.4
通讯作者：
Plana, Nuria
中科院分区：
文献类型：
--
作者：
Girona, Josefa;Rodriguez-Borjabad, Celia;Plana, Nuria
背景：家族性高胆固醇血症（FH）在儿童中被低估。与低密度脂蛋白受体（LDLR）功能相关的血浆生物标志物可以帮助识别FH儿童。结论：我们的目的是评估FH儿童与对照儿童（CCh）相比，LDLR诱导降解物（IDOL）、可溶性LDLR（sLDLR）和前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）血浆浓度的临床价值。这是一项在大学医院脂质室进行的横断面研究。参与者为177名儿童，分为FH（n = 77）和CCh（n = 100）。主要结果是IDOL，sLDLR，和PCSK 9血浆浓度的变化儿童组之间的次要结果是IDOL，sLDLR，和PCSK 9和血脂之间的关联确定的二维核磁共振。结果：与CCh相比，在FH的IDOL水平较高（P = 0.007）。在FH中PCSK 9水平升高（P <0.001）。各组sLDLR水平差异无统计学意义。IDOL与总胆固醇、LDL胆固醇和ApoB 100呈显著正相关，但与LDL颗粒数无关。然而，观察到与Lp（a）（P = .001）的稳健相关性。PCSK 9与LDL相关参数（包括颗粒数）的相关性最强。sLDLR与甘油三酯水平（P <0.001）和富含甘油三酯的颗粒相关，与LDL大小成反比。有趣的是，sLDLR与致动脉粥样硬化性血脂异常成分相关。IDOL浓度显示与Lp（a）水平的稳健相关性。研究与低密度脂蛋白受体表达相关的血浆生物标志物在FH中的作用是必要的。(C)2017年全国脂质协会。All rights reserved.
BACKGROUND: Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children.OBJECTIVES: We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh).METHODS: This was a cross-sectional study performed in a Lipid Unit from a University hospital. The participants were 177 children distributed into FH (n = 77) and CCh (n = 100). Main outcomes were changes in IDOL, sLDLR, and PCSK9 plasma concentrations between children groups; secondary outcomes were the association between IDOL, sLDLR, and PCSK9 and lipid profile determined by 2-dimensional nuclear magnetic resonance.RESULTS: The IDOL levels were higher in FH compared with CCh (P = .007). The PCSK9 levels were elevated in FH (P < .001). The sLDLR levels had no significant differences between groups. IDOL was significantly positively associated to total and LDL cholesterol and ApoB100 but not to LDL particle number. However, a robust correlation with Lp(a) (P = .001) was observed. PCSK9 had the strongest correlation with LDL-associated parameters including particle number. sLDLR was associated with triglyceride levels (P < .001) and triglyceride-rich particles and inversely to LDL size.CONCLUSIONS: The IDOL and PCSK9 plasma levels are significantly higher in FH children. Interestingly, sLDLR was associated with atherogenic dyslipidemia components. IDOL concentrations show a robust association with Lp(a) levels. To study the role of plasma biomarkers associated with LDLR expression in FH is warranted. (C) 2017 National Lipid Association. All rights reserved.