Affordable Access

Publisher Website

Apolipoprotein A-I Mutations and Clinical Evaluation-Chapter 2

Elsevier Inc.
DOI: 10.1016/b978-0-12-407867-3.00002-0
  • Apolipoprotein A-I
  • Mutation
  • Hdl Deficiency
  • Apolipoprotein A-I Deficiency
  • Abca1
  • Apolipoprotein A-I Milano (Apoa-Imilano)
  • Amyloidosis
  • Apolipoprotein Mimetic Peptide
  • Biology


Abstract Apolipoprotein (apo) A-I accounts for 70% of the total protein in high-density lipoprotein (HDL) and plays a key role in HDL biogenesis and function. Analyses of the apoA-I amino acid sequence have revealed that most of its 243 amino acid residues are grouped into amphipathic α-helices of 11 or 22 amino acids in length. Since the hydrophobic C-terminal domain (residues 190–243) of the human apoA-I molecule is critical for lipid binding, deletion of this segment reduces the ability of the protein to solubilize lipid. Sixteen different types of homozygous, compound heterozygous, and heterozygous apoA-I deficiencies, including large deficiency, inversion, frameshift, and nonsense mutations, have been reported. Most of the missense mutations causing low HDL cholesterolemia are associated with alterations to amino acids 143–187, forming α-helices 6–7 of apoA-I. Mutations in this region are accompanied by activation failure of lecithin:cholesterol acyltransferase (LCAT). Other point mutations leading to low HDL cholesterolemia include ApoA-I(S36A), (K107del), (R173C)Milano, (L178P), and (E235del)Nichinan. Twenty-one mutations that cause amyloidosis have been reported. The hereditary amyloidogenic mutations are clustered within amino acids 26−107 and 154−178 of apoA-I. ApoA-I (R151C)Paris and ApoA-I (R173C)Milano are rare cysteine variants that can form dimers. ApoA-IMilano, in particular, has been proven to exert anti-atherogenic effects in animal studies and small clinical trials. Although there are difficulties associated with its formulation, clinical applications are expected.

There are no comments yet on this publication. Be the first to share your thoughts.


Seen <100 times