Clinical implications of the apolipoprotein E polymorphism and genetic variants: current methods for apo E phenotyping

There is agreement about the influence of the genetic apolipoprotein (apo E) polymorphism on plasma lipid and apoprotein levels in man. Whereas the association of the apo E2 isoform with primary dysbetalipoproteinemia and hyperlipoproteinemia type III is well established, the plasma- and LDL-cholesterol lowering effects of apo E2 and the phenomenon of apo E4 raising these parameters on the development of coronary heart disease is still a matter of controversial discussion. Despite these uncertainties the knowledge of an individual's apo E phenotype may provide additional information in future to judge its risk to develop atherosclerosis. From a variety of methods meanwhile described to analyze the polymorphism and evaluate the apo E phenotype the author has modified three procedures to apply to different questions concerning apo E isoform analysis. They concern the visualization of the apo E pattern in diluted solutions and those containing high salt concentrations, the apo E phenotyping on a large scale basis from whole plasma avoiding a possible misinterpretation by a thrombin fragment of apo E and finally the search for new apo E variants with a high resolution system on immobilized pH gradient gels.