TECHNIQUES FOR THE DETERMINATION OF GENES INVOLVED IN LIPID/LIPOPROTEIN DISORDERS

随着分子生物学的进步，与 脂质/脂蛋白紊乱（特别是动脉粥样硬化性心血管疾病 疾病，[CVD]）最近已被鉴定和表征。我们有 一直在研究载脂蛋白（a）（apo[a]）及其产物的基因， a），以改善对病人的诊断，并更好地了解 参与心血管疾病发展的致病事件。 最近，我们在载脂蛋白（a）表型分型方面进行了技术改进， 适用于分离和免疫印迹的大蛋白质， 将军我们发现，大的蛋白质分子，如 采用CHEF脉冲场分离apo（a）， 凝胶电泳最初是为了分离 大的DNA分子我们还开发了一种快速廉价的 免疫印迹法是基于向下毛细作用的免疫印迹法。在 合作临床研究发现， 载脂蛋白（a）亚型与患者血栓栓塞事件的发生 系统性红斑狼疮目前正在进行更多的研究， 探讨各种载脂蛋白（a）亚型之间的可能联系， 在甲状腺状态极端变化的患者中的纤维蛋白溶解。

With advancements in molecular biology, genes associated with lipid/lipoprotein disorders (in particular, atherosclerotic cardiovascular disease, [CVD]) have been recently identified and characterized. We have been studying the gene for apolipoprotein(a) (apo[a]) and its product, apo(a), for improved diagnosis of patients and for better understanding of pathogenic events involved in the development of cardiovascular disease. Recently, we made technical improvements in apo(a) phenotyping with applicability to the separation and immunoblotting of large proteins in general. We showed that large protein molecules such as the isoforms of apo(a) can be efficiently separated by the CHEF version of pulsed-field gel electrophoresis that was originally developed for the separation of large DNA molecules. We also developed a rapid and inexpensive immunoblotting method that is based on downward capillary action. In collaborative clinical studies we discovered specific associations between apo(a) isoforms and the occurrence of thromboembolic events in patients with systemic lupus erythematosus. Additional studies are now under way to explore possible associations between various apo(a) isoforms and fibrinolysis in patients having extreme variations in thyroid status.