Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a).

Abstract

Patients with terminal renal insufficiency suffer from an increased incidence of atherosclerotic diseases. Elevated plasma concentrations of lipoprotein(a) ILp(a)I have been established as a genetically controlled risk factor for these diseases. Variable alleles at the apo(a) gene locus determine to a large extent the Lp(a) concentration in the general population. In addition, other genetic and nongenetic factors also contribute to the plasma concentrations of Lp(a).We therefore investigated Apo(a) phenotypes and Lp(a) plasma concentrations in a large group of patients with endstage renal disease (ESRD) and in a control group. Lp(a) concentrations were significantly elevated in ESRD patients (20.1±20.3 mg/dl) as compared with the controls (12.1±15.5 mg/dl, P < 0.001). However, no difference was found in apo(a) isoform frequency between the ESRD group and the controls. Interestingly, only patients with large size apo(a) isoforms exhibited two-to fourfold elevated levels of Lp(a), whereas the small-size isoforms had similar concentrations in ESRD patients and controls. Beside elevated Lp(a) concentrations, ESRD patients had lower levels of plasma cholesterol and apolipoprotein B.These results show that elevated Lp(a) plasma levels might significantly contribute to the risk for atherosclerotic diseases in ESRD. They further indicate that nongenetic factors related to renal insufficiency or other genes beside the apo(a) structural gene locus must be responsible for the high Lp(a) levels. (J. Clin. Invest. 1993. 91:397-401.) Key words: lipoprotein(a) -apolipoprotein(a) phenotypes * terminal renal insufficiency -end-stage renal disease * atherosclerosis

Apolipoprotein(a) isoform-specific changes of lipoprotein(a) after kidney transplantation

“…7,8 In the present study, the relative decrease of Lp(a) was different for the various groups of HMW apo(a) isoforms: the combined results of both HMW isoforms in the HMW phenotype group showed a decrease of Lp(a) to 68% from the value before transplantation, which was less pronounced than in the group of HMW isoforms in the LMW phenotype group (decrease to 22%). However, when we consider the absolute differences for Lp(a) levels between before and after kidney transplantation, we can observe a difference of 10.4 mg/dl for the HMW apo(a) isoform in patients with LMW apo(a) phenotypes.…”

“…Those with low molecular weight (LMW) apo(a) phenotypes showed similar Lp(a) concentrations than matched controls. 7,8 Although these findings were recently supported by two studies, 9,10 three other reports did not confirm our observation and described an elevation of Lp(a) in all apo(a) phenotype groups. 11 -13 Since our original observation suggested a rare example of a disease influence on the allele-specific expression of a protein in humans, we have reinvestigated the problem using a more rigorous approach.…”

“…7,8 In our studies Lp(a) showed a relative increase only in hemodialysis patients with the so-called HMW apo(a) phenotypes when compared to phenotypematched controls, but not in those with LMW apo(a) phenotypes. This interesting but still unexplained phenomenon was confirmed by two recent reports 9,10 and is supported by a phenotype-specific decrease of Lp(a) following kidney transplantation: in a prospective study including 154 patients, the average Lp(a) plasma concentration decreased during the first 3 weeks following transplantation only in the group of patients with HMW apo(a) phenotypes, but remained unchanged in those with LMW apo(a) types.…”

“…This strongly supports the finding that the elevation of Lp(a) in hemodialysis patients is apo(a) genotype-related. 7,8 Material and methods…”

High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection": The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein

“…A commercially available Lp(a) standard from Immuno AG (Vienna, Austria) served as a control. Concentrations of apoB in cell media and ultracentrifugation density gradient fractions were measured by a recently described double-antibody ELISA (Dieplinger et al, 1993). An affinity-purified rabbit polyclonal antibody against human apoB was used for coating.…”