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.
