Apolipoprotein E - Gene

Gene

The protein, ApoE, is mapped to chromosome 19 in a cluster with Apolipoprotein C1 and the Apolipoprotein C2. The APOE gene consists of four exons and three introns, totaling 3597 base pairs.

ApoE is polymorphic with three major isoforms: ApoE2 (cys130, cys176), ApoE3 (cys130, arg176), and ApoE4 (arg130, arg176). Although these allelic forms differ from each other by only one or two amino acids at positions 130 and 176, these differences alter apoE structure and function. These have physiological consequences:

• E2 (rs7412) is found in approximately 7 percent of the population . E2 is associated with the genetic disorder hyperlipoproteinemia type III and with both increased and decreased risk for atherosclerosis. Individuals with an E2/E2 combination may clear dietary fat slowly and be at greater risk for early vascular disease and type III hyperlipoproteinemia—94.4% of such patients are E2/E2, while only ∼2% of E2/E2 develop the disease. So other environmental and genetic factors are likely to be involved.

• E3 (rs429358) is found in approximately 79 percent of the population . It is considered the "neutral" Apo E genotype.

• E4 is found in approximately 14 percent of the population . E4 has been implicated in atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth.

ApoE is transcriptionally activated by the liver X receptor (an important regulator of cholesterol, fatty acid, and glucose homeostasis) and peroxisome proliferator-activated receptorγ, nuclear receptors that form heterodimers with Retinoid X receptors. In melanocytic cells APOE gene expression may be regulated by MITF.