Disease Characteristic
ApoE is a transporter protein, which is involved in lipoprotein metabolism and cardiovascular disease. Apo E genotyping is used for individuals with high cholesterol and triglyceride levels to examine for genetic component for these lipid abnormalities. This polymorphic gene has three major alleles, ApoE2, ApoE3, and ApoE4, which translate into three isoforms of the protein: normal - ApoE3; dysfunctional - ApoE2 and ApoE4.
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How Common is ApoE abnormality?
Apo E2 and Apo E4 homozygosity has been shown in a fair number of patients with hereditary hyperlipoproteinemia and hypercholesterolemia. Apo E4 homozygotes have also been reported in patients suffering from Alzheimer’s disease.
Genes and Mutations (Genotype-Phenotype Relationships)
The APOE gene is mapped to chromosome 19 in a cluster with APOC1 and APOC2. Isoforms ApoE2, ApoE3, and ApoE4 are product of different mutations resulting in substitutions at positions 112 and 158 and have profound physiological consequences.
Mutations and penetrance
Isoform E3 is Normal.
Isoform E2 is associated with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis.
Isoform E4 has been implicated in atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth.
Phenotypes
Elevated cholesterol and triglyceride levels
Criteria for Genetic Testing
When family members have ApoE e2/e2 or ApoE e4/e4
When you see xanthomas (yellowish lesions) on their skin suspected of
Type III hyperlipoproteinemia
High cholesterol and triglyceride levels in family
Symptoms of progressive dementia