Individuals with familial hyperlipoproteinemia
Dementia of unknown cause
Suspected Alzheimer's disease
Apolipoprotein E4-Allele ApoE
Clinical Features
The apolipoprotein E (ApoE) is involved in a complex regulatory mechanism stabilizing the serum lipid levels via binding of ApoE to its receptors on hepatocytes. In case of a mutation of the ApoE gene, the reduced receptor binding of ApoE can result in dyslipoproteinemias. At present, three isoforms of ApoE are known, E2, E3 und E4. The allelic frequencies of these isoforms are for E2: 11%, for E3: 72% and for E4: 17 %.
Isoform E2 is associated with a higher risk for developing arteriosclerosis. Heterozygous carriers of the ApoE E2 allele exhibit dyslipidemia whereas homozygosity predisposes to type III hyperlipidemia in 1-4% of cases. Heterozygosity for the isoform E4 can lead to type V hyperlipidemia. In individuals with clinical symptoms of Alzheimer's disease, the presence of one or two ApoE4 alleles supports the diagnosis.
Genetic Information
The apolipoprotein E gene is localized on chromosome 19. The isoforms differ with regard to the nucleotide sequence of codon 112 and 158:
E2 cysteine/cysteine; E3 cysteine/arginine; E4 arginine/arginine.
Prevalence
E2: 1 : 9
E3: 1 : 1,4
E4: 1 : 5
Diagnostic
Indication
Method
PCR and restriction enzyme digestion and DHPLC
Sample Requirement
2 - 4 ml of EDTA-Blut
Duration
1 - 2 weeks