Apolipoprotein E variation in patients with hyperlipidaemia: DNA and protein phenotyping.

Two patients with marked elevation of plasma and very low density lipoprotein (VLDL) lipids were investigated to establish the molecular basis of their hyperlipidaemia. In one the demonstration of the apolipoprotein E 2/2 phenotype substantiated the diagnosis of type III hyperlipidaemia. In the other the E4/3 phenotype excluded this diagnosis. In both cases oligonucleotide probing of amplified DNA and isoelectric focusing (IEF) of apo VLDL identified the correct apolipoprotein E phenotype as defined by peptide mapping and IEF of purified apolipoprotein E after modification with iodoacetic acid. Probing of amplified DNA clearly distinguishes the three common variants of apolipoprotein E (E2, E3, E4) and facilitates the diagnosis of type III hyperlipidaemia.