Apolipoprotein E polymorphism has no independent effect on plasma levels of lipoprotein(a)

Previous studies show conflicting results concerning an influence of apolipoprotein E (apo E) phenotype on lipoprotein(a) (Lp(a)) plasma levels. We speculated that it is not the apo E phenotype itself but rather its effect on plasma lipid concentrations that might influence Lp(a) levels. In 1562 subjects concentrations of triglycerides, LDL-cholesterol and Lp(a) were measured by standard laboratory methods. Apo(a) and apo E isoforms were determined by sodium dodecyl sulfate gel electrophoresis and isoelectric focusing, respectively, followed by immunoblotting. An univariate analysis revealed a significant influence of apo(a) isoforms, apo E phenotype, triglycerides and LDL-cholesterol on Lp(a) plasma levels (ANOVA: P < 0.001, P < 0.02, P < 0.001 and P < 0.001, respectively). In a multivariate analysis, however, the influence of the apo E phenotype was no longer significant (P>0.10), whereas apo(a) isoforms, LDL-cholesterol quintiles and triglyceride quintiles explained 29.2, 2.8 and 1.0% of the variation of the Lp(a) levels (for all three variables: P < 0.001). We conclude that apo E polymorphism does not exert an independent effect on Lp(a) concentrations. Any influence is mediated through the effect of apo E polymorphism on plasma lipids.