HYPERLIPOPROTEINEMIA, MIXED (COMBINED HYPERLIPIDEMIA IIB)

APOA1, APOE, LIPC

Description

SCIENTIFIC BACKGROUND

In combined hyperlipidemia (hyperlipidemia type IIb according to the Fredrickson classification), triglycerides and LDL (low density lipoprotein) cholesterol are elevated and HDL cholesterol is often lowered. Total cholesterol levels may be in the normal range, but are often elevated. In gel electrophoresis, strong beta and pre-beta bands are shown and the alpha band is visible. The fasting serum is slightly cloudy. Xanthomas are tendinous and tuberous.

 

In the broadest sense, combined hyperlipidemia can be linked to pathogenic variants of three genes:

 

  1. Apolipoprotein E (APOE) is a recognition site for receptors involved in the elimination of VLDL (very-low density lipoprotein) remnants and chylomicrons. Variants in the APOE gene lead to dysbetalipoproteinemia (Fredrickson type III). The three isoforms APOE E2, E3 and E4, which result from the combination of two nucleotide positions (c.388 and c.526), play a major role here. In rare cases other variants in apo E can cause combined hyperlipidemia. The risk of premature cardiovascular disease is greatly increased. The prevalence is about 1:10,000.

 

  1. Lipase C (LIPC), also called hepatic triglyceride lipase (HTGL), is synthesized in the liver. It converts IDL (intermediate density lipoproteins) into LDL (low density lipoproteins) and thus plays an important role in the regulation of triglycerides in the blood. Pathogenic variants of the LIPC gene cause a very rare (approximately 1:1,000,000) autosomal recessive inherited hepatic lipase deficiency.

 

  1. Apolipoprotein A1 (APOA1), a cofactor for lecithin-cholesterol acyltransferase, is synthesized in the liver and small intestine and promotes cholesterol efflux from the cell. In very rare cases, combined hyperlipidemia is caused by variants in the APOA1 gene. Clinical presentations of an APOA1 deficiency are opaque corneas and coronary heart disease from the 4th to the 7th decade of life.

 

References

März et al. 2017, Herz 42:449 / Koopal et al. 2016, J Clin Lipidol 11:12 / Ramasamy 2016, Clin Chim Acta 454:143 / Marais et al. 2014, Crit Rev Clin Lab Sci 51:46 / Jawalekar 2012, Biochem Physiol 1:1

GENES

APOA1, APOE, LIPC

ASSOCIATED TESTS

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