Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

You are here: Molecular Genetics » Dysbetalipoproteinemia

Dysbetalipoproteinemia (Type III Hyperlipidemia) [E78.2]

OMIM numbers: 107741 (APOE)

Dr. med. Hanns-Georg Klein

Scientific Background

Familial dysbetalipoproteinemia (type III hyperlipidemia according to Fredrickson, autosomal recessive, incidence approx. 1 in 2,000) is based on an impaired metabolism of chylomicrons and VLDL remnants. Their absorption into the liver occurs by apolipoprotein E (Apo E). Remnants are degradation products of the plasma lipoprotein metabolism and belong to the most atherogenic lipoprotein particles. Therefore, affected patients bear a high vascular risk (artery occlusive disease, coronary heart disease, stroke). Tuberous or tendinous xanthomas occur frequently. Palmar crease xanthomas are pathognomonic. Biochemically, an increased serum concentration of ?-VLDL can be observed concomitant with an increase of triglycerides and total body cholesterol. Dietary control is the preferred treatment. However, studies have shown that the administration of HMG-CoA reductase inhibitors achieves good results as well.


The molecular mechanisms of type III hyperlipidemia have not been fully understood so far. Homozygosity for the E2 allele of apolipoprotein E seems to be a precondition. Two polymorphisms in the APOE gene lead to the amino acid substitutions Cys112Arg (rs429358) and Arg158Cys (rs7412), resulting in three isoforms: ApoE2, ApoE3 and ApoE4 (allele frequencies: E2: 11%, E3: 72% and E4: 17%). ApoE2 has a lowered LDL receptor-binding ability, which leads to an enrichment of remnants and thus to an increase of total cholesterol and triglycerides. However, only approx. 4% of individuals who are homozygous for APOE2 develop type III hyperlipidemia. Secondary factors like hypothyreosis, a lack of estrogen, adipositas, alcohol abuse or diabetes are necessary. Studies demonstrate a potential role of variants of the apolipoprotein A-V gene (e.g. -1131T->G) as modifier.