Rader - Figure 5 - Molecular causes of elevated LDL-C Text

Rader - Figure 5 - Molecular causes of elevated LDL-C

In another presentation in this publication Dr. McGowan has discussed the molecular causes of elevated LDL-C.  This Figure reviews the five documented molecular causes of elevated LDL-C levels.

  • mutations in the LDL receptor, the primary receptor that binds and removes LDL-C from the circulation;
  • mutations in ApoB, and particularly in the receptor binding region of ApoB that mediates the binding of the LDL particle to the LDL receptor; 
  • mutations in PCSK9, specifically gain of function mutations that activate PCSK9 and resulted in targeting LDL receptors for degradation; 
  • mutations in LDL RAP1 or the ARH protein, which is involved with LDL receptor trafficking; 
  • finally, not shown schematically on this Fig, sitosterolemia due to mutations in ABCG5 or ABCG8 transporters can also result in very severe hypercholesterolemia.

These are the known genetic causes of substantial elevations in LDL-C levels.

Rader J Clin Lipidol. 2012;