A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and cutaneous amyloidosis

Kamran Hamidi Asl, Juris J. Liepnieks, Masaaki Nakamura, Frank Parker, Merrill D. Benson

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An American kindred was found to have hereditary amyloidosis with cutaneous and cardiac involvement. Characterization of fibrils isolated from skin identified the amyloid protein as the N-terminal 90 to 100 residues of apolipoprotein A-1. Sequence of the apolipoprotein A-1 gene was normal except for a G/C transversion at position 1638 which predicts an Arg to Pro substitution at residue 173. This mutation, unlike previously described amyloidogenic mutations is not in the N-terminal fragment which is incorporated into the fibril. The mutation is at the same residue as in apolipoprotein A-1 Milano (Arg173Cys) which does not result in amyloid formation. Decreased plasma HDL cholesterol levels in carriers of the Arg173Pro mutation suggest an increased rate of catabolism as has been shown for the amyloidogenic Gly26Arg mutation. This suggests that altered metabolism caused by the mutation may be a significant factor in apolipoprotein A-1 fibrillogenesis.

Original languageEnglish (US)
Pages (from-to)584-588
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Apr 13 1999


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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