Apolipoprotein E

 

 

Apolipoprotein E Genotyping (ApoE)

Background:
Apolipoprotein E is involved in the secretion, synthesis, and, metabolism of lipoproteins in the circulation.  The gene for apolipoprotein E (APOE) maps to chromosome 19q13.2.  This gene is polymorphic.  The three common alleles, e2, e3, and e4, differ only by a single amino acid substitution as indicated below.  Average allele frequencies in various populations are indicated in parentheses; however, these values may differ between ethnic populations.

e2: cys112, cys158 (11%)

e3: cys112, arg158 (72%)

e4: arg112, arg158 (17%)

These apoE variants differ in function by their ligand-binding affinity for apoE receptors and are involved in the maintenance of cholesterol and triglycerides in the blood.

Reasons for Referral:

APOE genotyping may provide additional information toward the risk or diagnosis of:

  • Familial hyperlipoproteinemia type III (dysbetalipoproteinemia)
  • Coronary artery disease
  • Cholesterol
  • High blood pressure
  • Alzheimer disease (AD) , APOE and PS2 genes.

In Iranian population, we found a positive association of the PS2 –A allele and the PS2 +A/–A genotype  with AD patients. The APOE4 allele was strongly associated with AD (p c = 0.000002).

 Response to rivastigmine therapy in AD

Patients with the PS2 +A/–A genotype and bigenic genotypes of PS2+A/–A _ APO e3/e3 and +A/–A _ e3/ e4 were the best responders to Exelon therapy, and those with the PS2+A/+A and APO e3/ e4 genotypes were the worst responders. Conclusion: Our findings suggest that the PS2 and APOE4 alleles and genotypes affect both AD risk and response to rivastigmine therapy (Zamani et al 2011, Pharmacogenetic Study on the Effect of Rivastigmine on PS2 and APOE Genes in Iranian Alzheimer Patients.Dement Geriatr Cogn Disord Extra;1:180–189).

Method:
Direct DNA analysis: PCR-based assay with restriction enzyme digestion (HhaI) will identify the three most common APOE alleles, e2, e3, and e4.  Less common variants will not be detected and PS2 alleles +A and –A.

Interpretation and Reporting:

The patient’s genotype will be reported.

The following clinical associations with APOE genotypes have been reported but are not diagnostic:

  • e2,e2:  hyperlipoproteinemia type III (dysbetalipoproteinemia)  1-5% develop disease
  • e4,e4;  increased risk for coronary artery disease (elevated plasma cholesterol, LDL, ApoB, LpA)
  • e3,e4: Increased risk of elevated systolic blood pressure and early myocardial infarction

A single e2 or e4 allele can predispose a patient to elevated plasma cholesterol and triglyceridemia.

Analytic Time:  14 days.

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