Figure 1.

Apolipoprotein E (APOE) gene pleiotropic roles may be explained by its exceptional epigenetic properties. The APOE ε2/ε3/ε4 alleles are produced by two cytosine-phosphate-guanine (CpG)-altering SNPs (rs429358 and rs7412) in the core region of the APOE CpG islands. APOE ε4 carriers have the greatest number of CpG dinucleotide sites, while APOE ε2 carriers have the smallest number, so methylation levels for most CpG sites are in the order of APOE ε4 carriers > APOE ε3/ε3 > APOE ε2 carriers. In the promoter region, there is another SNP, rs405509. Furthermore, other epigenetics mechanisms are linked to the processing of primary miR-650 to mature miR-650 is mis regulated. miR-650 can significantly reduce the expression of APOE.