“Whoa! It's like Spotify but for academic articles.”

Instant Access to Thousands of Journals for just $40/month

Get 2 Weeks Free

Rare genetic causes of autosomal dominant or recessive hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a human inherited disorder of metabolism characterised by increased serum low‐density lipoprotein (LDL) cholesterol. It is caused by defects in the LDL‐receptor pathway that impair normal uptake and clearance of LDL by the liver. The commonest cause of FH is mutations in LDLR, the gene for the LDL receptor, but defects also occur in APOB that encodes its major protein ligand. More recently, defects in two other genes, LDLRAP1 and PCSK9, have been found in patients with FH and investigation of these has shed new light on the functioning and complexity of the LDL receptor pathway. Cells from patients with autosomal recessive hypercholesterolaemia (ARH) fail to internalise the LDL receptor because they carry two defective alleles of LDLRAP1, a gene that encodes a specific clathrin adaptor protein. PCSK9 encodes proprotein convertase subtilisin kexin type 9, a secreted protein that binds to the LDL receptor and promotes its degradation. Gain‐of function mutations in PCSK9 are autosomal dominant and cause hypercholesterolaemia because they increase the affinity of PCSK9 protein for the LDL receptor, whereas loss‐of‐function mutations reduce serum cholesterol because LDL‐receptor protein is exposed to reduced PCSK9‐mediated degradation. Thus, PCSK9 has become a new target for cholesterol‐lowering drug therapy. © 2010 IUBMB IUBMB Life, 62(2): 125–131, 2010 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png IUBMB Life Wiley

Loading next page...

You're reading a free preview. Subscribe to read the entire article.

And millions more from thousands of peer-reviewed journals, for just $40/month

Get 2 Weeks Free

To be the best researcher, you need access to the best research

  • With DeepDyve, you can stop worrying about how much articles cost, or if it's too much hassle to order — it's all at your fingertips. Your research is important and deserves the top content.
  • Read from thousands of the leading scholarly journals from Springer, Elsevier, Nature, IEEE, Wiley-Blackwell and more.
  • All the latest content is available, no embargo periods.

Stop missing out on the latest updates in your field

  • We’ll send you automatic email updates on the keywords and journals you tell us are most important to you.
  • There is a lot of content out there, so we help you sift through it and stay organized.