FREQUENCY OF PHENOTYPE-GENOTYPE DISCREPANCIES AT THE APOLIPOPROTEIN-ELOCUS IN A LARGE POPULATION STUDY

Apolipoprotein E (apoE) genotypes were determined in a random subset o f 1041 subjects enrolled in the Framingham Offspring Study by using DN A amplification followed by restriction isotyping. The results were co mpared with the apoE phenotypes previously assessed by isoelectric foc using. Discrepancies in apoE allele assignment were found in 98 subjec ts (9.4%). Both genotype and phenotype were reassessed in these subjec ts, Genotype misclassification was observed in 20 subjects, whereas th e initial phenotype assignment was modified in 46 subjects. No concord ance between apoE phenotype and genotype remained in 32 subjects (3.07 %). Both methods resulted in similar apoE allele frequencies. Furtherm ore, no differences were observed regarding the average allelic effect on total cholesterol, LDL cholesterol, or HDL cholesterol concentrati ons; however, a significant difference was noted on triglyceride conce ntrations. Our results indicate that most discrepancies between genoty pe and phenotype assessment of apoE polymorphism were due to sample mi shandling, data entry, and technical difficulties rather than true dis cordances.