Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Apolipoprotein B

Mutations that result in defective apolipoprotein B cause a rare but severe disease, abetalipoproteinemia. More common are mutations with impared LDL receptor binding and elavated LDL cholesterol.

Epidemiology

The prevalance of the homozygous form is 1:1.000.000. The allel frequency is 1:500.

Gene Structure

Apolipoprotein B (ApoB) exists in two different versions called ApoB100 and ApoB48. In enterocytes a posttranscriptional modification of the mRNA takes place. As a result of this modification a stop codon is generated and translation is aborted when 48% of the protein is synthesized. There is no LDL rececptor ligant in ApoB48.

Phenotype

Phenotypicaly there is no difference beween mutations affecting ligand region in ApoB100 and LDL rececptor mutations. Patients have a significant hypercholesterinemia. In lipidelektrophoresis we see a predomination of LDL particles According to Fredrickson this hyperlipemia is classifyed typ II. The chance for oxydation of these particles and by this way the risk for cardiovascular disease is hight.

Pathology

ApoB100 is secreted by hepatocytes togesther with VLDL. Enterocytes secrete ApoB48 in chylomikrones. Functioning ApoB100 can be reabsorbed by hepatocytes via LDL rececptor. Chylomikrons containing ApoB48 hepatocytes by other mechanisms. Mutations in ApoB100 affecting the ligand lead to increase of cholesterol rich LDL particels. The effect is just the same as in LDL rececptor mutations.

Interpretation

Apolipoprotein B mutations and LDL rececptor mutation should be screened together.

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 20 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
Autosomal dominant hypercholesterolemia 2
APOB
Hypobetalipoproteinemia
ANGPTL3
APOB

References:

1.

Vrablík M et al. (2001) Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis.

[^]
2.

None (2003) Familial hypobetalipoproteinemia: a review.

[^]
3.

Whitfield AJ et al. (2004) Lipid disorders and mutations in the APOB gene.

[^]
4.

Schonfeld G et al. (2005) Familial hypobetalipoproteinemia: genetics and metabolism.

[^]
5.

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

[^]
6.

Soria LF et al. (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.

[^]
7.

Orphanet article

Orphanet ID 121386 [^]
8.

NCBI article

NCBI 338 [^]
9.

OMIM.ORG article

Omim 107730 [^]
10.

Wikipedia article

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