GENOTYPING COMPARED WITH PROTEIN PHENOTYPING OF THE COMMON APOLIPOPROTEIN-E POLYMORPHISM

Apolipoprotein E (apo E) genotypes have been determined in 460 Danish men, with the use of the polymerase chain reaction (PCR) to amplify a 244 base pair fragment spanning the first-base polymorphic sites in th e codons of amino acids 112 and 158 followed by restriction endonuclea se cleavage. The results were compared with the apo E phenotypes previ ously determined by isoelectric focusing (IEF) of delipidated plasma, not pretreated with neuraminidase, followed by apo E specific immunobl otting. Conflicting results were found in only 9 cases (2.0%) and in e ach case only with respect to one allele. Five of the discrepancies ca n be explained, post hoc, by technical difficulties with the IEF metho d ('faint bands'). A possible cause of the other 4 discrepancies is th e presence of rare mutations. Our findings in this large study are rea ssuring, since, if appreciable and systematic misclassification of gen otypes do occur by using IEF, as has been reported from some laborator ies, it may influence the validity of genetic epidemiological studies.