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Apolipoprotein B100 - APOB

Hypercholesterolemia TYP IIa

Clinical Features

Familial hypercholesterolemia (FH) is one of the most common monogenetic metabolic diseases of the liver. In order to reduce cholesterol levels in the blood, LDL as the main transport vehicle of cholesterol in the circulation interacts with LDL receptors on hepatocytes. The efficiency of LDL receptor binding is determined by coupling of ApoB100 to LDL.

There are two forms of familial hypercholesterolemia:

• Mutations in the LDL receptor gene are associated with elevated cholesterol levels up to more than 500 mg/dl

• Mutations in the ApoB100 gene are associated with moderate elevation of cholesterol levels

Heterozygous mutations in the ApoB100 gene result in cholesterol levels of 200-450 mg/dl, homozygous mutations may result in cholesterol levels of more than 450 mg/dl.

Genetic Information

The ApoB100 (apolipoprotein B100) gene is localized on chromosome 2 (2p24.1).
The four most frequent mutations of the ApoB100 gene are
APOB p.3543His>Tyr(H3543Y)
APOB p.3500Arg>Gln(R3500Q)
APOB p.3500ARG>Trp(R3500W)
APOB p.3531Arg>Cys(R3531C)

Prevalence

p.3543H>Y: 1 : 120
p.3500R>Q: 1 : 500
p.3531R>C: 1 : 3 000

Diagnostic