Role of fibrinolytic parameters and plasminogen activator inhibitor 1 (PAI-1) promoter polymorphism on premature atherosclerosis in SLE patients

Abstract

Premature atherosclerosis has been recognized as a major co-morbid condition in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of tPA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor) antigen concentrations and 4G/5G polymorphism of the PAI-1 gene on the development of atherosclerosis in SLE patients. One hundred and six SLE patients, 28 Takayasu arteritis (TA) patients and 98 healthy control subjects (HCs) were studied. PAI-1 and tPA antigen levels were measured by ELISA method. PAI-1 gene polymorphism was determined by using allele-specific PCR method. SLE patients had a significantly higher frequency (22.6%) of plaque (p = 0.01) and higher IMT (p=0.04) compared with HCs respectively. Only age at disease onset was associated with plaque formation in multivariate regression analysis (p = 0.001). Plasma tPA ag levels in SLE patients were significantly higher compared with HCs (p = 0.005) and PAI-1 ag levels were significantly higher compared with TA patients (p = 0.03). There were no significant differences between study groups in both genotype distribution and allele frequencies of PAI-1 gene, but SLE patients with 4G/4G genotype had higher IMT (p = 0.02) calcium scoring (p = 0.006) compared with 4G5G/5G5G genotypes. The present study suggests that measuring fibrinolytic parameters would have little additional benefit beyond traditional and novel risk factors in predicting coronary artery disease (CAD).