Apo E variants in patients with type III hyperlipoproteinemia

Area of Science:

• Genetics
• Biochemistry
• Molecular Biology

Background:

• Type III hyperlipoproteinemia (HLP III) is a genetic disorder characterized by impaired catabolism of chylomicron and very low-density lipoprotein (VLDL) remnants.
• The apolipoprotein E2 (apo E2) allele (Cys112, Cys158) is most commonly associated with HLP III, but other rare apo E gene mutations have also been implicated.

Purpose of the Study:

• To investigate the prevalence of rare apo E variants in a Spanish population of HLP III patients.
• To evaluate the concordance between isoelectric focusing (IEF) for apo E phenotyping and polymerase chain reaction (PCR) with restriction enzyme analysis for genotyping.

Main Methods:

• Apo E phenotypes were determined using isoelectric focusing (IEF).
• Apo E genotypes were analyzed by PCR amplification of the apo E gene followed by restriction enzyme analysis.
• DNA sequencing of the receptor-binding domain of the apo E gene was performed for subjects with discordant results between IEF and PCR.

Main Results:

• A lack of concordance between IEF and PCR methods was observed in 73.3% of the 15 HLP III patients studied.
• DNA sequencing revealed carriers of epsilon 3(Arg136-->Ser) and epsilon 2(Gly127-->Asp) alleles in patients with discordant results.
• Discrepancies included patients identified as apo E2/E2 by IEF but not by PCR, and patients with E3/E3 genotype and normal DNA sequence in the receptor-binding domain.

Conclusions:

• Multiple distinct apolipoprotein E genotypes are associated with HLP III in the studied population.
• Mutations at positions 127 and 136 of the apo E gene may be prevalent in Spain and contribute to HLP III pathogenesis.