University of Washington, Seattle, Washington 98109, USA.
Clin Chim Acta. 2010 Sep 6;411(17-18):1279-83. doi: 10.1016/j.cca.2010.05.012. Epub 2010 May 19.
Lp(a) is a proatherogenic lipoprotein that may also be prothrombotic. Apo(a) size isoforms have differential effects on fibrinolysis. Whereas Lp(a) concentrations have been linked to venous thromboembolic disease (VTE) risk, apo(a) polymorphisms in VTE have not been studied.
We used a standardized high resolution agarose gel electrophoresis technique to determine apo(a) isoform size, and a Lp(a) immunoassay insensitive to apo(a) size to measure Lp(a) concentration in 46 men with VTE and 46 age-matched healthy controls.
Apo(a) isoform distribution in VTE cases and controls was bimodal and VTE patients tended to have more medium-sized isoforms K(4)-(19-27) (54.3% vs. 34.8%, p=0.06). Cases and controls had the same median predominant apo(a) size isoform (23.5 K(4) repeats) and comparable Lp(a) concentrations. However, subgroup analysis based on apo(a) isoform size (K(4)< or =23 or K(4)> or =24) revealed that cases in the K(4)> or =24 subgroup had higher Lp(a) concentrations than the controls in this isofrom subgroup (14.5 mmol vs. 6.6 mmol, p=0.029). Also, dyslipoproteinemia (smaller LDL and HDL particles, higher LDL and lower HDL parameters) was strongly associated with VTE only in this larger apo(a) isoform group.
These observations provide the first evidence that determination of apo(a) isoforms may provide useful novel insights into VTE risk.
Lp(a) 是一种促动脉粥样硬化的脂蛋白,也可能具有促血栓形成作用。载脂蛋白(apo)a 大小的同种型对纤溶有不同的影响。虽然 Lp(a) 浓度与静脉血栓栓塞性疾病(VTE)风险有关,但 VTE 中的 apo(a) 多态性尚未得到研究。
我们使用标准化的高分辨率琼脂糖凝胶电泳技术来确定 apo(a) 同种型大小,并使用一种对 apo(a) 大小不敏感的 Lp(a) 免疫测定法来测量 46 例 VTE 患者和 46 名年龄匹配的健康对照者的 Lp(a) 浓度。
VTE 病例和对照组的 apo(a) 同种型分布呈双峰型,VTE 患者倾向于具有更多的中等大小同种型 K(4)-(19-27)(54.3% vs. 34.8%,p=0.06)。病例和对照组具有相同的中位数主要 apo(a) 大小同种型(23.5 K(4) 重复)和可比的 Lp(a) 浓度。然而,基于 apo(a) 同种型大小(K(4)< 或 =23 或 K(4)> 或 =24)的亚组分析显示,在 K(4)> 或 =24 亚组中,病例的 Lp(a) 浓度高于该同种型亚组中的对照组(14.5 mmol vs. 6.6 mmol,p=0.029)。此外,脂蛋白异常血症(较小的 LDL 和 HDL 颗粒,较高的 LDL 和较低的 HDL 参数)仅与较大的 apo(a) 同种型组中的 VTE 强烈相关。
这些观察结果首次提供了证据,表明 apo(a) 同种型的测定可能为 VTE 风险提供有用的新见解。