COMMON AND RARE GENOTYPES OF HUMAN APOLIPOPROTEIN-E 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 phenot yping by isoelectric focusing (IEF). The polymerase chain reaction (PC R) method allows the detection of common and several rare allelic apo E variants not detected by IEF. We propose a genotyping procedure for apo E that characterizes a given allele on the basis of amplification of specific sequences of the gene followed by the action of restrictio n endonucleases. When the nucleotide change does not lead to a restric tion site, PCR-directed mutagenesis creates the discriminant site, and the differentiation of the three common alleles and five rare variant s is possible. We present here profiles of common alleles and of three rare alleles, Weisgraber [Cys(112)/Asp(127)/Cys(158)], Christchurch [ Cys(112)/Ser(136)/Arg(158)], and a new rare variant [Cys(112)/Leu(142) /Cys(158)].