Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro

Daniel Coriu, Angela Dispenzieri, Fred J. Stevens, Charles L. Murphy, Shuching Wang, Deborah T. Weiss, Alan Solomon

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Apolipoprotein A-I amyloidosis (AApo A-I) is an inherited systemic disease that results from pathologic deposition in tissues of fibrils composed of Apo A-I-related molecules. This disorder has been linked to mutations occurring within the coding region of the Apo A-I gene and heretofore, nine such variants had been described. Recently, a tenth alteration was found in an Italian population where the substitution of proline for leucine at position 75 (Leu75Pro) was associated with amyloid deposits in the liver. We now report our studies on a patient of different ethnicity who has hepatic amyloidosis and a similar mutation in the amyloidogenic precursor protein, as evidenced from analyses ofgenomic Apo A-I-encoding DNA. Additionally, fibrils extracted from the liver and characterized chemically were found to be composed almost exclusively of a ∼96 residue N-terminal Apo A-I fragment that contained the Leu75Pro substitution. RFLP analyses revealed that the patient was heterozygous for this mutation; however, < 10% of the plasma Apo A-I consisted of the aberrant protein while the remainder had the normal (wild-type) sequence. Our findings provide further evidence that the Leu75Pro variant is associated with a predominant hepatic phenotype and can occur in individuals of diverse ethnic backgrounds.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalAmyloid
Volume10
Issue number4
StatePublished - Dec 2003

Fingerprint

Apolipoprotein A-I
Amyloidosis
Liver
Mutation
Amyloidogenic Proteins
Amyloid Plaques
Proline
Leucine
Restriction Fragment Length Polymorphisms
Phenotype
DNA
Population
Genes
Proteins

Keywords

  • Amyloidosis
  • Apolipoprotein A-I
  • Hepatic amyloid
  • Mass spectrometry
  • Variant gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Coriu, D., Dispenzieri, A., Stevens, F. J., Murphy, C. L., Wang, S., Weiss, D. T., & Solomon, A. (2003). Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro. Amyloid, 10(4), 215-223.

Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro. / Coriu, Daniel; Dispenzieri, Angela; Stevens, Fred J.; Murphy, Charles L.; Wang, Shuching; Weiss, Deborah T.; Solomon, Alan.

In: Amyloid, Vol. 10, No. 4, 12.2003, p. 215-223.

Research output: Contribution to journalArticle

Coriu, D, Dispenzieri, A, Stevens, FJ, Murphy, CL, Wang, S, Weiss, DT & Solomon, A 2003, 'Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro', Amyloid, vol. 10, no. 4, pp. 215-223.
Coriu D, Dispenzieri A, Stevens FJ, Murphy CL, Wang S, Weiss DT et al. Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro. Amyloid. 2003 Dec;10(4):215-223.
Coriu, Daniel ; Dispenzieri, Angela ; Stevens, Fred J. ; Murphy, Charles L. ; Wang, Shuching ; Weiss, Deborah T. ; Solomon, Alan. / Hepatic amyloidosis resulting from deposition of the apolipoprotein A-I variant Leu75Pro. In: Amyloid. 2003 ; Vol. 10, No. 4. pp. 215-223.
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