Apolipoprotein E

Polymorphisms of apolipoprotein E; the subtypes E2, E3, and E4; have been associated with hyperlipidaemia and Alzheimer disease. In many other pathologies, correlations are not so strong.

Epidemiology

Apolipoprotein E mutations can be found throughout the world. In Germany allel frequencies are: wildtype E3 80%, E2 and E4 10%.There some more rare mutation affecting the ligand region of the gene have been found. These mutation have importance in lipid disorders. There is no evidence abaut correlation of these mutations to Alzheimer's disease.

Gene Structure

The gene consists of 3 exons. Preapolipoprotein E is the result translation. It contains 317 amino acids. 18 amino acids will be cleaved off the N-terminal end during secretion. The mature peptide contains exon 3 and partly exons 2 codons. Physiologically relevant is the receptor ligand coded in exon 3.

Phenotype

The influence of E2-allel on clinical signs is dose dependent. In case of E2/E2 genotype the rare form of hyperlipimia may be deduced. According to Fredrickson this hyperlipemia is classifyed typ III. This form is characterized by IDL and remnants.In Diabetes there seems to be a correlation of E2 allel and albuminuria.The E4 allel on the opposite is correlated with Alzheimer's disease.

Pathology

Apolipoprotein E is included in lipoproteins rich in triglycerides (chylomikrons und VLDL). Apolipoprotein E holds the ligand for the receptor in hepatocytes. If this ligand part of the protein is mutated the above mentioned lipoproteins will increase in plasma. This takes place when the E2 allel is present.

Interpretation

Epidemiologically there is a strong correlation between E2 genotype and lipid disorders. Nevertheless there are broad individual differences modifyed by environment and some other genes. That way an effective dietary education can be deduced by the evidence of the E2 allel.The mechanism leading to Alzheimer's diesease is not quite cleare yet. But apolipoprotein genotyping can provide useful additional information for early diagnosis.

Genetests:

Clinic	Method	Carrier testing
	Turnaround	5 days
	Specimen type	genomic DNA

Clinic	Method	Massive parallel sequencing
	Turnaround	25 days
	Specimen type	genomic DNA

Clinic	Method	Genomic sequencing of the entire coding region
	Turnaround	5 days
	Specimen type	genomic DNA

Clinic	Method	Target mutation analysis
	Turnaround	20 days
	Specimen type	genomic DNA

Related Diseases:

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