Analysis of the apolipoprotein(a) size polymorphism in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by an increased incidence of vascular disease which is only partially explained by traditional risk factors. Previous reports suggested that the level of lipoprotein(a) [Lp(a)], a particle linked to atherothrombotic disorders, is increased in patients with SLE. However, whether there are any differences in the distribution of apolipoprotein(a) [apo(a)] phenotypes between SLE patients and healthy controls remain to be determined. To address this issue, Lp(a) levels and apo(a) isoform size were analyzed in a total of 54 patients with SLE and in 108 age- and gender-matched healthy controls. SLE patients showed Lp(a) levels [median (interquartile range): 25.3 (6.5-51.0) vs. 9.5 (4.6-25.9) mg/dl, P=0.0109)] and a percentage of subjects with at least one small-sized apo(a) isoform (< or =25 K-IV repeats) significantly higher than controls (44.44% vs. 25.92%, P=0.0277). Multiple regression analysis adjusting for age, gender, disease duration, kidney involvement, the presence of active disease, as well as the carriage of at least one small apo(a) isoform revealed that only small apo(a) phenotypes were significant predictors of Lp(a) levels in SLE patients (P=0.0001). We conclude that genetic factors related to apo(a) size are a major determinant of elevated Lp(a) levels in patients with SLE. As small apo(a) phenotypes have been related to adverse vascular effects, it is feasible that small apo(a) isoforms may be a useful biological marker in the assessment of vascular risk in patients with SLE.