The missing ApoE allele

The human apoE gene (APOE, GenBank accession AF261279) shows a common polymorphism, with the three epsilon 2, epsilon 3 and epsilon 4 alleles resulting from the haplotypes of two C -> T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the epsilon 2, epsilon 3 and epsilon 4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as epsilon 3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of epsilon 3r remains to be explained, and requires further investigation.