Common and Rare Genotypes of Human ApolipoproteinE Determined by Specific Restriction Profiles of Polymerase Chain Reaction-Amplified DNA

The three common isoforms of human apolipoprotein E (apo E) differ at positions 112 and 158 and are named E3, E4, and E2 according to phenotypingby isoelectric focus-ing (IEF). The potymerase chain reaction (PCR) method allows the detection of commonand several rare allelicapo E variants not detected by IEF. We propose a genotyping procedurefor apo E that characterizesa given allele on the basis of amplification of specific sequences of the gene followed by the action of restrictionendonucleases. When the nucleotide change does not lead to a restriction site, PCR-directed mutagenesis creates the discnminant site, and the differentiationof the three common alleles and five rare variants is possible. We present here profiles of com-mon alleles and of three rare alleles, Weisgraber [Cys112/ Asp1/Cys1], Chnstchurch [Cys112/Ser1/Arg1], and a new rare variant [Cys112/Leu142/Cys1]