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Clinical Chemistry 42: 1817-1823, 1996;
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Clinical Chemistry, Vol 42, 1817-1823, Copyright © 1996 by American Association for Clinical Chemistry

Frequency of phenotype-genotype discrepancies at the apolipoprotein E locus in a large population study

C Lahoz, D Osgood, PW Wilson, EJ Schaefer and JM Ordovas
Lipid Metabolism Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. lahoz- li@hnrc.tufts.edu

Apolipoprotein E (apoE) genotypes were determined in a random subset of 1041 subjects enrolled in the Framingham Offspring Study by using DNA amplification followed by restriction isotyping. The results were compared with the apoE phenotypes previously assessed by isoelectric focusing. Discrepancies in apoE allele assignment were found in 98 subjects (9.4%). Both genotype and phenotype were reassessed in these subjects. Genotype misclassification was observed in 20 subjects, whereas the initial phenotype assignment was modified in 46 subjects. No concordance between apoE phenotype and genotype remained in 32 subjects (3.07%). Both methods resulted in similar apoE allele frequencies. Furthermore, no differences were observed regarding the average allelic effect on total cholesterol, LDL cholesterol, or HDL cholesterol concentrations; however, a significant difference was noted on triglyceride concentrations. Our results indicate that most discrepancies between genotype and phenotype assessment of apoE polymorphism were due to sample mishandling, data entry, and technical difficulties rather than true discordances.


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