Genetics of the apolipoprotein E system in man

Area of Science:

• Human Genetics
• Molecular Biology
• Biochemistry

Background:

• Apolipoprotein E (Apo E) exhibits polymorphism in humans, controlled by two distinct genetic loci: Apo E-N/D and Apo E4.
• The Apo E-N/D locus has codominant alleles (Apo E(n), Apo E(d)), while the Apo E4 locus has dominant (Apo E4(+)) and recessive (Apo E4(o)) alleles.

Purpose of the Study:

• To investigate the association and linkage between the Apo E-N/D and Apo E4 genetic loci.
• To explore potential models explaining the observed Apo E phenotypes and their genetic underpinnings.

Main Methods:

• Frequency distribution analysis of Apo E phenotypes in the human population.
• Segregation analysis of Apo E phenotypes in informative matings.
• Evaluation of different genetic models to explain observed data.

Main Results:

• A highly significant association (P ≈ 1%) was found between the Apo E-N/D and Apo E4 systems.
• The Apo E4-(+) variant was significantly more frequent in the Apo E-N phenotype compared to Apo E-ND.
• The Apo E-D/-E4(+) phenotypic combination was not observed, suggesting linkage or interaction.

Conclusions:

• The segregation patterns support close linkage between the Apo E-N/D and Apo E4 loci.
• Multiple genetic models, including linkage disequilibrium or differential gene expression, can explain the findings.
• The Apo E-N/D locus may influence posttranslational modification of Apo E, impacting its molecular weight.