High plasma levels of apo(a) fragments in Caucasians and African-Americans with end-stage renal disease

Implications for plasma Lp(a) assay

Vincent Mooser, Santica M. Marcovina, Jinping Wang, Helen H. Hobbs

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Apolipoprotein(a) [apo(a)] is a plasma glycoprotein that is highly polymorphic in size due to differences in the number of a tandemly arrayed cysteine-rich repeat called kringle (K)4 at its N-terminus. Most plasma apo(a) is covalently attached to apolipoprotein B-100 and circulates as part of lipoprotein(a) [Lp(a)]. A fraction of apo(a) circulates free of lipoproteins. Almost all of the free apo(a) consists of fragments containing variable numbers of K4 repeats derived from the N-terminal region. Previously we provided evidence suggesting that the apo(a) fragments present in human plasma are the source of the apo(a) fragments in human urine. If this were the case, it would be expected that plasma levels of fragments would be higher in subjects with end-stage renal disease (ESRD). In this paper we quantified the levels of apo(a) fragments and plasma Lp(a) in 26 Caucasian and 26 African-American subjects with ESRD and 52 healthy subjects matched for race, sex and the size of the apo(a) isoforms. The plasma levels of apo(a) fragments and Lp(a) were both higher in the ESRD subjects. In addition, the ratio of apo(a) fragments to total immunodetectable apo(a) was increased in ESRD. To determine how much the increase in the apo(a) fragments contributed to the increase in plasma Lp(a) in ESRD, the plasma Lp(a) levels were measured employing two different anti-apo(a) enzyme-linked immunoabsorption assays (ELISA). One assay detected both free and bound apo(a), whereas the other assay detected only bound apo(a). Although the plasma levels of apo(a) in the ESRD subjects tended to be higher using the assay that detected both fragments and full-length apo(a), the increase was modest. Thus, although a greater proportion of the apo(a) in ESRD plasma circulates as fragments, most of the elevation in plasma levels of Lp(a) associated with renal insufficiency is due to an increase in intact Lp(a).

Original languageEnglish (US)
Pages (from-to)387-392
Number of pages6
JournalClinical Genetics
Volume52
Issue number5
StatePublished - Nov 1997

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Apoprotein(a)
Lipoprotein(a)
African Americans
Chronic Kidney Failure
Kringles
Apolipoprotein B-100

Keywords

  • African-Americans
  • Apolipoprotein(a)
  • Caucasians
  • ELISA
  • End-stage renal disease
  • Hemodialysis
  • Lipoprotein(a)
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

High plasma levels of apo(a) fragments in Caucasians and African-Americans with end-stage renal disease : Implications for plasma Lp(a) assay. / Mooser, Vincent; Marcovina, Santica M.; Wang, Jinping; Hobbs, Helen H.

In: Clinical Genetics, Vol. 52, No. 5, 11.1997, p. 387-392.

Research output: Contribution to journalArticle

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