Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

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:

Arteriosclerosis
APOB
APOE
HABP2
LDLR
LPA
MTHFR
PON1
SLC3A1
Alzheimer disease
APOE
APP
CLU
CYP2D6
HFE
Chylomicronemia
APOA5
APOC2
APOE
GPIHBP1
LPL
Hypertriglyceridemia
APOA5
APOE
Combined lipase deficiency
LMF1
GPIHBP1
LIPC
LIPE
LPL
Plasma triglyceride level quantitative trait locus
ANGPTL4
Transient infantile hypertriglyceridemia
GPD1
Lipoprotein glomerulopathy
APOE
Sea-blue histiocyte disease
APOE
Age-related macula degeneration 01
APOE
ARMS2
C2
C3
CFH
CFHR1
CFHR3
KCNT2
Combined familial hyperlipidemia with VLDL overproduction
APOE
GCKR
OSBPL10
USF1

References:

1.

Parhofer KG et al. (2006) Thematic review series: patient-oriented research. What we have learned about VLDL and LDL metabolism from human kinetics studies.

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2.

Lusis AJ et al. (2004) Genetic basis of atherosclerosis: part I: new genes and pathways.

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3.

Kadotani H et al. (2001) Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults.

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4.

Takahashi S et al. (2004) The very low-density lipoprotein (VLDL) receptor: characterization and functions as a peripheral lipoprotein receptor.

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5.

Mahley RW et al. (2006) Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease.

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6.

OMIM.ORG article

Omim 107741 [^]
7.

Orphanet article

Orphanet ID 121390 [^]
8.

NCBI article

NCBI 348 [^]
9.

Wikipedia article

Wikipedia EN (Apolipoprotein E) [^]
Update: April 29, 2019