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Kidney Int. 2004 Feb;65(2):606-12.

The apolipoprotein(a) size polymorphism is associated with nephrotic syndrome.

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  • 1Institute of Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, Austria.Florian.Kronenberg@uibk.ac.at

Abstract

BACKGROUND:

The atherogenic serum lipoprotein(a) [Lp(a)] is significantly elevated in patients with nephrotic syndrome. The underlying mechanism for this elevation is poorly understood.

METHODS:

We investigated in 207 patients with nondiabetic nephrotic syndrome and 274 controls whether the apolipoprotein(a) [apo(a)] kringle-IV repeat polymorphism explains the elevated Lp(a) levels in these patients.

RESULTS:

Patients showed a tremendous elevation of Lp(a) concentrations when compared to controls (mean 60.4 vs. 20.0 mg/dL and median 29.8 vs. 6.4 mg/dL, P < 0.0001). Primary and secondary causes contributed to this elevation. The primary causes became apparent by a markedly elevated number of low-molecular-weight apo(a) phenotypes which are usually associated with high Lp(a) levels. This frequency was 35.7% in patients compared to only 24.8% in controls (P= 0.009). In addition, secondary causes by the pathogenetic mechanisms of the nephrotic syndrome itself resulted in a different increase of Lp(a) in the various apo(a) isoform groups. Based on the measured Lp(a) concentrations in each subject, we calculated separately the Lp(a) concentrations arising from the two expressed isoforms by estimating the relative proportion of the two serum isoforms in the sodium dodecyl sulfate (SDS) agarose gel electrophoresis. Low-molecular-weight isoforms were associated with 40% to 75% elevated Lp(a) concentrations when compared to matched isoforms from controls. High-molecular-weight apo(a) isoforms showed 100% to 500% elevated Lp(a) levels compared to matched isoforms from controls. The severity of the nephrotic syndrome as well as the degree of renal impairment did not influence the Lp(a) concentrations.

CONCLUSION:

The tremendously increased Lp(a) levels in nephrotic syndrome ar caused by primary genetic as well as disease-related mechanisms.

PMID:
14717931
[PubMed - indexed for MEDLINE]
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