PCSK9 gene mutations can have profound effects on plasma LDL-C levels1
PCSK9 Loss of Function Mutations
Increase LDLR levels on the surface of the hepatocyte, which leads to an increase in LDL clearance, resulting in low plasma LDL-C levels2,3
PCSK9 Gain of Function Mutations
Decrease LDLR levels on the surface of the hepatocyte, which leads to a reduction in LDL clearance, resulting in high plasma LDL-C levels2,3
HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; LDLR = low-density lipoprotein receptor; PCSK9 = proprotein convertase subtilisin/kexin type 9.
- Horton JD, Cohen JC, Hobbs HH. J Lipid Res. 2009;50(suppl):S172-S177.
- Abifadel M, Rabes J-P, Devilliers M, et al. Hum Mutat. 2009;30:520-529.
- Steinberg D, Witzum JL. PNAS. 2009;106:9546-9547.